Particle separation flow channel unit and particle separation device

Abstract

The present invention can independently control the upstream particle sorting section and the downstream particle sorting section of a single channel unit for microparticle sorting. The present invention provides a channel unit for microparticle sorting, which includes: a first particle sorting section; a fluid holding container, which is located downstream of the first particle sorting section and can hold fluid; and a second particle sorting section, which is located downstream of the fluid holding container. The fluid holding container is fluidically connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section. The amount of fluid held by the fluid holding container changes according to the difference in flow rates before and after the container. In addition, the present invention provides a microparticle sorting device including a channel unit for microparticle sorting.

Description

Technical Field

[0001] The present technology relates to a particle sorting flow channel unit and a particle sorting device. More specifically, the present technology relates to a particle sorting flow channel unit including two particle sorting parts and a particle sorting device including the particle sorting flow channel unit. Background Art

[0002] So far, various devices for sorting microparticles have been developed. For example, in a microparticle sorting system for a flow cytometer, a laminar flow including a sample liquid containing cells and a sheath liquid is discharged from a hole formed in a flow cell or a microchip. A predetermined vibration is applied to the laminar flow during the discharge, thereby forming droplets. Depending on whether the target microparticles are contained, the moving direction of the formed droplets is electrically controlled, and the target microparticles are sorted.

[0003] As described above, a technology for sorting target particles in a microchip without forming droplets has also been developed. For example, the following patent document 1 describes "a microchip comprising: a sample liquid introduction channel, through which a sample liquid containing particles flows; at least one pair of sheath liquid introduction channels, which merge with the sample liquid introduction channel from both sides and introduce the sheath liquid around the sample liquid; a merging channel, which is connected to the sample liquid introduction channel and the sheath liquid introduction channel, and the liquid flowing through these channels merges and flows through the merging channel; a negative pressure suction section, which is connected to the merging channel and sucks the particles to be recovered; and at least one pair of processing channels, which are arranged on both sides of the negative pressure suction section and are connected to the merging channel (claim 1). In the microchip, the target particles are recovered by suction to the negative pressure suction section.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: Japanese Patent Application Publication No. 2012-127922 Summary of the invention

[0007] Problems to be solved by the present invention

[0008] From the particles sorted according to the presence or absence of a specific characteristic, it may be necessary to further sort particles having another characteristic. In addition, in the case where the particles sorted by a sorting process contain unexpected particles, it may be necessary to further improve the purity of the target particles. In order to meet such a demand, for example, it is conceivable that another particle sorting microchip is further connected downstream of a particle sorting microchip. That is, it is conceivable that a liquid containing particles sorted in the particle sorting section of the previous particle sorting microchip is introduced into the next particle sorting microchip, and particle sorting is performed in the particle sorting section of the next particle sorting microchip.

[0009] However, in a particle sorting flow channel unit obtained by simply connecting the two particle sorting microchips together, for example, through a flow channel (e.g., a tube), the flow rate in one particle sorting microchip affects the flow rate in the other particle sorting microchip. This influence makes it difficult to independently control the flow rates of the particle sorting sections in the two particle sorting microchips.

[0010] An object of the present technology is to provide a technology for controlling an upstream particle sorting section and a downstream particle sorting section independently of each other in one microparticle sorting flow channel unit.

[0011] Solution to the problem

[0012] The present inventors have found that the above-mentioned problems can be solved by a flow channel unit having a specific configuration.

[0013] That is, the present technology provides a particle sorting flow channel unit, comprising:

[0014] a first particle sorting section; a fluid storage container located downstream of the first particle sorting section and capable of storing a fluid; and a second particle sorting section located downstream of the fluid storage container, wherein

[0015] The fluid storage container is fluidly connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, and

[0016] The fluid storage container is configured so that the fluid storage capacity in the container changes according to the flow rate difference before and after the container.

[0017] The fluid storage container may be a container that suppresses the influence of flow rate fluctuation in the flow channel upstream or downstream of the fluid storage container on the flow rate in the flow channel downstream or upstream of the fluid storage container.

[0018] According to one embodiment of the present technology, the particle sorting flow channel unit may include a first particle sorting microchip and a second particle sorting microchip, and

[0019] The first particle sorting section may be provided in a first microparticle sorting microchip, and the second particle sorting section may be provided in a second microparticle sorting microchip.

[0020] A pump may be disposed between the fluid discharge port and the fluid supply port, and a fluid storage container may be disposed upstream of the pump.

[0021] The fluid storage container may be used to independently control the flow rate of the fluid flowing through the first particle sorting section and the flow rate of the fluid flowing through the second particle sorting section.

[0022] The fluid storage container can be used to reduce the influence of the pulsating flow of the fluid flowing through any one of the first particle sorting section and the second particle sorting section on the flow rate in the other particle sorting section.

[0023] In one aspect of the present technology, a particle sorting flow channel unit may include an upstream particle sorting microchip and a downstream particle sorting microchip, the upstream particle sorting microchip may be provided with a first particle sorting section and at least one fluid discharge port, the downstream particle sorting microchip may be provided with a second particle sorting section and at least one fluid supply port, and a fluid storage container may be provided on a flow channel that fluidically connects at least one fluid discharge port with at least one fluid supply port.

[0024] In one aspect of the present technology, the fluid storage container may be used as a container for recovering microparticles sorted in the first particle sorting section.

[0025] In another aspect of the present technology, a particle recovery container that recovers particles sorted in the first particle sorting section may be provided downstream of the fluid storage container.

[0026] In another aspect of the present technology, the volume of the fluid storage space in the particle recovery container can be constant.

[0027] The particle sorting flow channel unit may include a first particle sorting microchip and a second particle sorting microchip, and

[0028] The fluid storage container can be provided in either microchip of the two particle sorting microchips.

[0029] At least one of the first particle sorting section and the second particle sorting section may include: a main flow channel through which a fluid containing particles flows; a branch flow channel branching from the main flow channel; and a particle sorting flow channel coaxial with the main flow channel.

[0030] The fluid storage container may be configured to be able to store a fluid having an amount greater than or equal to a value obtained by multiplying an absolute value of a flow rate difference before and after the container by a time for which the fluid flows in the particle sorting flow channel unit.

[0031] In addition, the present technology also provides a particle sorting device, including a particle sorting flow channel unit, the particle sorting flow channel unit includes: a first particle sorting part; a fluid storage container, located downstream of the first particle sorting part and capable of storing fluid; and a second particle sorting part, located downstream of the fluid storage container, wherein:

[0032] The fluid storage container is fluidly connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, and

[0033] The fluid storage container is configured so that the fluid storage capacity in the container changes according to the flow rate difference before and after the container.

[0034] The particle sorting device can independently control the flow rate of the fluid flowing through the first particle sorting section and the flow rate of the fluid flowing through the second particle sorting section. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 is a diagram showing an example of a particle sorting microchip;

[0036] Figure 2 is a diagram showing a particle sorting section in a particle sorting microchip;

[0037] Figure 3 is a diagram showing a configuration example of two microparticle sorting microchips connected together;

[0038] Figure 4 is a diagram showing a configuration example of a microparticle sorting flow channel unit of the present technology;

[0039] Figure 5 is a diagram showing a configuration example of a microparticle sorting flow channel unit of the present technology;

[0040] Figure 6 is a diagram showing a configuration example of a microparticle sorting flow channel unit of the present technology;

[0041] Figure 7 is a diagram showing a configuration example of a microparticle sorting device of the present technology;

[0042] Figure 8 is a diagram showing a configuration example of a microparticle sorting flow channel unit of the present technology;

[0043] Fig. 9 is a diagram showing the measurement results of flow rate;

[0044] Fig.10 is a diagram showing the measurement results of flow rate;

[0045] Fig.11A is a schematic perspective view of the vicinity of an orifice portion of a microparticle sorting microchip;

[0046] Fig. 11B is a schematic cross-sectional view of an orifice portion of a particle sorting microchip;

[0047] Fig. 12A is a schematic perspective view of the vicinity of an orifice portion of a microparticle sorting microchip;

[0048] Fig. 12B It is a schematic cross-sectional view of the orifice portion of the particle sorting microchip. DETAILED DESCRIPTION

[0049] Hereinafter, a description will be given of preferred embodiments for implementing the present technology. Note that the embodiments described below are representative embodiments of the present technology, and the scope of the present technology is not limited to these embodiments. Note that the present technology will be described in the following order.

[0050] 1. Related technologies

[0051] 2. First embodiment (particle sorting flow channel unit)

[0052] (1) Description of the First Embodiment

[0053] (2) First Example of the First Embodiment (Microparticle Sorting Flow Channel Unit)

[0054] (3) Second Example of the First Embodiment (Microparticle Sorting Flow Channel Unit)

[0055] (4) Third Example of the First Embodiment (Microparticle Sorting Flow Channel Unit)

[0056] 3. Second embodiment (particle sorting device)

[0057] 4. Examples

[0058] 1. Related technologies

[0059] The following will refer to Figure 1 An example of a technique for sorting target particles in a microchip is described. Figure 1 is a schematic diagram of an example of a particle sorting microchip.

[0060] like Figure 1 As shown, the microchip 100 is provided with a sample liquid inlet 101 and a sheath liquid inlet 103. From these inlets, the sample liquid and the sheath liquid are introduced into a sample liquid flow channel 102 and a sheath liquid flow channel 104, respectively. Microparticles are contained in the sample liquid.

[0061] The sample liquid and the sheath liquid merge in the merging section 112 to form a laminar flow in which the sample liquid is surrounded by the sheath liquid. The laminar flow flows toward the particle sorting section 107 through the main flow channel 105 .

[0062] The main flow channel 105 is provided with a detection area 106. In the detection area 106, the microparticles in the sample liquid are irradiated with light. Based on the fluorescence and / or scattered light generated by the light irradiation, it can be determined whether the microparticles are microparticles to be recovered. One position in the detection area 106 can be irradiated with one light, or each of the multiple positions in the detection area 106 can be irradiated with light. For example, the microchip 100 can be configured so that each of two different positions in the detection area 106 is irradiated with light (that is, there are two positions in the detection area 106 to be irradiated with light). In this case, for example, it can be determined whether the microparticles are microparticles to be recovered based on the light (e.g., fluorescence and / or scattered light) generated by irradiating the microparticles with light at one position. In addition, the speed of the microparticles in the flow channel can also be calculated based on the difference between the detection time of the light generated by the light irradiation at one position and the detection time of the light generated by the light irradiation at another position. For the calculation, the distance between the two irradiation positions can be predetermined, and the speed of the microparticles can be determined based on the difference between the two detection times and the distance. In addition, based on the speed, the time to reach the particle sorting section 107 described below can be accurately predicted. The arrival time is accurately predicted, thereby optimizing the formation timing of the flow entering the particle sorting flow channel 109. In addition, in the case where the difference between the time when a specific particle arrives at the particle sorting section 107 and the time when the particle before or after the specific particle arrives at the particle sorting section 107 is less than or equal to a predetermined threshold, it can also be determined not to sort the specific particle. In the case where the distance between a specific particle and the particle before or after the specific particle is small, the possibility that the particles before or after the specific particle are recovered together with the suction of the specific particle increases. By determining not to sort the specific particles when the possibility of the particles being recovered together is high, the particles before or after the specific particles can be prevented from being recovered. Therefore, the purity of the target particles in the recovered particles can be improved. For example, a specific example of a microchip that irradiates each of two different positions in the detection area 106 with light and a device including the microchip is described in Japanese Patent Application Publication No. 2014-202573.

[0063] In the particle sorting section 107 in the microchip 100 , the laminar flow flowing through the main flow channel 105 is divided into two branch flow channels 108 and flows. Figure 1 The particle sorting section 107 shown includes two branch flow channels 108, but the number of branch flow channels is not limited to two. The particle sorting section 107 may be provided with, for example, one or more (for example, two, three, four, etc.) branch flow channels. Figure 1 As shown, the branch flow channel may be configured to branch in a Y shape on one plane, or may be configured to branch in three dimensions.

[0064] In addition, in the particle sorting section 107, only when the microparticles to be recovered flow, a flow entering the particle sorting channel 109 is formed, and the microparticles are recovered. The formation of the flow entering the particle sorting channel 109 can be performed, for example, by generating a negative pressure in the particle sorting channel 109. In order to generate a negative pressure, for example, an actuator can be attached to the outside of the microchip 100 so that the wall of the particle sorting channel 109 can be deformed. Due to the deformation of the wall, the internal space of the particle sorting channel 109 changes, and a negative pressure can be generated. The actuator can be, for example, a piezoelectric actuator. When the microparticles are sucked into the particle sorting channel 109, the sample liquid forming a laminar flow or the sample liquid and the sheath liquid forming a laminar flow can also flow into the particle sorting channel 109. In this way, the microparticles are sorted in the particle sorting section 107.

[0065] Figure 2 FIG. 1 shows an enlarged view of the particle sorting section 107. Figure 2 As shown, the main channel 105 and the particle sorting channel 109 are connected to each other via an orifice portion 120 coaxial with the main channel 105. The microparticles to be recovered flow to the particle sorting channel 109 through the orifice portion 120. In addition, the orifice portion 120 may be provided with a gate inlet 121 to prevent the unrecovered microparticles from entering the particle sorting channel 109 through the orifice portion 120. A sheath liquid is introduced from the gate inlet 121, and a flow from the orifice portion 120 to the main channel 105 is formed by a portion of the introduced sheath liquid, thereby preventing the unrecovered microparticles from entering the particle sorting channel 109. Note that the remaining portion of the introduced sheath liquid flows to the particle sorting channel 109.

[0066] Fig.11A and Fig. 11B An enlarged view of the vicinity of the orifice portion 120 is shown. Fig.11A 1 is a schematic perspective view of the vicinity of the orifice portion 120 . Fig. 11B is a cross-sectional view of the orifice portion 120. The cross-sectional view is a schematic cross-sectional view in a plane passing through the center line of the gate inlet 121 and the center line of the orifice portion 120. The orifice portion 120 includes a flow channel 120a on the detection area 106 side (hereinafter also referred to as the upstream orifice portion flow channel 120a), a flow channel 120b on the particle sorting flow channel 109 side (hereinafter also referred to as the downstream orifice portion flow channel 120b), and a connecting portion 120c between the orifice portion 120 and the gate inlet 121. The gate inlet 121 is arranged to be substantially perpendicular to the axis of the flow channel of the orifice portion 120. Fig.11A and Fig. 11B In the embodiment, two gate inlets 121 are provided to face each other substantially at the center position of the orifice portion 120, but only one gate inlet may be provided.

[0067] The shape and size of the cross section of the upstream orifice flow passage 120a may be the same as the shape and size of the downstream orifice flow passage 120b. Fig.11A and Fig. 11B As shown, the cross-section of the upstream orifice flow passage 120a and the cross-section of the downstream orifice flow passage 120b can be substantially circular with the same size. Alternatively, both cross-sections can be rectangular (eg, square or oblong) with the same size.

[0068] The shape and / or size of the cross section of the upstream orifice portion flow passage 120a may be different from the shape and / or size of the downstream orifice portion flow passage 120b. Fig. 12A and Fig. 12B An example is shown in FIG. 1 in which the dimensions of the two flow channels are different from each other. Fig. 12A and Fig. 12B As shown, the orifice portion 130 includes a flow channel 130a on the detection area 106 side (hereinafter also referred to as the upstream orifice portion flow channel 130a), a flow channel 130b on the particle sorting flow channel 109 side (hereinafter referred to as the downstream orifice portion flow channel 130b), and a connecting portion 130c between the orifice portion 130 and the gate inlet 121. The cross-section of the upstream orifice portion flow channel 130a and the cross-section of the downstream orifice portion flow channel 130b both have a substantially circular shape, but the diameter of the latter cross-section is larger than the diameter of the former cross-section. By making the cross-sectional diameter of the latter larger than the cross-sectional diameter of the former, compared with the case where the two diameters are the same, it is possible to more effectively prevent the particles sorted in the particle sorting flow channel 109 immediately after the particle sorting operation from being discharged into the main flow channel 105 through the orifice portion 130 due to the above-mentioned negative pressure.

[0069] For example, when the cross-section of the upstream orifice flow channel 130a and the cross-section of the downstream orifice flow channel 130b are both rectangular, by making the area of ​​the latter cross-section larger than the area of ​​the former cross-section, the recovered particles can be more effectively prevented from being discharged into the main channel 105 through the orifice 130 as described above.

[0070] The laminar flow to the branch channel 108 can be discharged to the outside of the microchip at the branch channel end 110. In addition, the particles recovered in the particle sorting channel 109 can be discharged to the outside of the microchip at the particle sorting channel end 111. In this way, the target particles are sorted by the microchip 100.

[0071] In order to further sort out particles with specific characteristics from the particles sorted by the particle sorting microchip (for example, the above-mentioned microchip 100), or to improve the purity of the particles with specific characteristics, it can be imagined that another particle sorting microchip is further connected downstream of the particle sorting microchip (for example, downstream of the particle sorting flow channel end 111 of the microchip 100).

[0072] However, in the case where two particle sorting microchips are connected together, for example, by a flow channel (e.g., a tube), the flow rate in the flow channel forming the particle sorting section in one particle sorting microchip will have an influence on the flow rate in the flow channel forming the particle sorting section in the other particle sorting microchip. This influence makes it difficult to independently control the flow rates in the two particle sorting sections. This will be described below with reference to Figure 3 Give a description.

[0073] Figure 3 An example of a particle sorting flow channel unit including two particle sorting microchips whose flow channels are connected together is shown. Figure 3 The particle sorting flow channel unit 300 shown includes two particle sorting microchips 100a and 100b, and these particle sorting microchips 100a and 100b are connected together, for example, via a flow channel connecting member 330 (for example, a tube). The particle sorting microchip 100a and the particle sorting microchip 100b are both similar to those described above. Figure 1 and Figure 2 The particle sorting microchip 100 described is the same. The particle sorting flow channel end 111a of the microchip 100a (i.e., the fluid discharge port from the microchip 100a) is connected to one end of the flow channel connecting member 330, and the other end of the flow channel connecting member 330 is connected to the sample liquid inlet 101b of the microchip 100b (i.e., the fluid supply port of the microchip 100b). In addition, a pump 370 is provided upstream of the sample liquid inlet 101b to introduce the sample liquid from the sample liquid inlet 101b into the microchip 100b at a predetermined flow rate.

[0074] exist Figure 3 In the particle sorting flow channel unit 300 shown, in the case where the liquid flows from the upstream particle sorting microchip 100a to the downstream particle sorting microchip 100b without driving the pump 370, the discharge flow rate from the particle sorting flow channel end 111a of the microchip 100a is the same as the introduction flow rate to the sample liquid inlet 101b of the microchip 100b. In this case, the discharge flow rate and the introduction flow rate cannot be controlled independently of each other. Therefore, the flow rate in the particle sorting flow channel 109a and the flow rate in the sample liquid flow channel 102b cannot be controlled independently of each other.

[0075] In addition, when the pump 370 is driven to control the flow rate in the sample liquid flow channel 102b, the flow rate fluctuation (e.g., pulsating flow, etc.) caused by the pump 370 may have an influence on the flow rate in the microchip 100a (specifically, the flow rate in the particle sorting flow channel 109a). This influence may also have an influence on the microparticle sorting in the particle sorting section 107a of the microchip 100a.

[0076] Similarly, the flow fluctuation in the microchip 100a may also affect the flow in the microchip 100b (specifically, the flow in the sample liquid flow channel 102b), and may also affect the microparticle sorting in the particle sorting section 107b of the microchip 100b.

[0077] As described above, in two particle sorting microchips such as Figure 3 When connected together as shown, it is difficult to independently control the flow rates in the two particle sorting sections included in these microchips.

[0078] The present inventors have found that the flow rates in the two particle sorting sections can be independently controlled by a particle sorting flow channel unit having a specific configuration. The configuration of the particle sorting flow channel unit will be described in detail below.

[0079] 2. First embodiment (particle sorting flow channel unit)

[0080] (1) Description of the First Embodiment

[0081] The present technology relates to a particle sorting flow channel unit, including: a first particle sorting section; a fluid storage container located downstream of the first particle sorting section and capable of storing fluid; and a second particle sorting section located downstream of the fluid storage container. The fluid storage container included in the flow channel unit is fluidically connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, and the fluid storage container is configured to change the fluid storage capacity in the container according to the flow rate difference before and after the container. The flow rates in the first particle sorting section and the second particle sorting section can be independently controlled by the fluid storage container.

[0082] The particle sorting flow channel unit of the present technology includes a first particle sorting section and a second particle sorting section. These particle sorting sections may be the same as or different from each other. The second particle sorting section is downstream of the first particle sorting section. That is, the fluid (for example, the fluid containing particles) passing through the first particle sorting section is subjected to particle sorting in the second particle sorting section. Therefore, from the particles sorted according to the presence or absence of a specific characteristic, particles having another characteristic can be further sorted. In addition, in the case where the particles sorted by a sorting process contain unexpected particles, the purity of the target particles can be further improved.

[0083] According to one embodiment of the present technology, the first particle sorting section and the second particle sorting section can be respectively arranged in two particle sorting microchips. In this embodiment, the fluid (specifically, the fluid containing particles) of the first particle sorting section arranged in the upstream particle sorting microchip is used to sort particles in the second particle sorting section arranged in the downstream particle sorting microchip. In the present technology, the upstream particle sorting microchip is also referred to as the first particle sorting microchip, and the downstream particle sorting microchip is also referred to as the second particle sorting microchip. That is, in this embodiment, the particle sorting flow channel unit includes a first particle sorting microchip and a second particle sorting microchip, and the first particle sorting section is arranged in the first particle sorting microchip, and the second particle sorting section is arranged in the second particle sorting microchip. Particle sorting can be performed in each microchip.

[0084] In this embodiment, at least one fluid discharge port is arranged in the upstream particle sorting microchip, and at least one fluid supply port is arranged in the downstream particle sorting microchip. At least one fluid discharge port and the fluid storage container can be fluidically connected together, and can be fluidically connected together, for example, by a flow channel connecting member (e.g., a tube). The fluid (specifically, the fluid containing particles) passing through the first particle sorting section can be discharged from at least one fluid discharge port to the outside of the upstream particle sorting microchip, and then travel to the fluid storage container through the flow channel connecting member. In addition, the fluid storage container and at least one fluid supply port can be fluidically connected together, and can be fluidically connected together, for example, by a flow channel connecting member (e.g., a tube). The fluid (specifically, the fluid containing particles) leaving the fluid storage container enters the downstream particle sorting microchip from at least one fluid supply port, and then travels to the second particle sorting section.

[0085] According to another embodiment of the present technology, the first particle sorting section and the second particle sorting section can be arranged in a particle sorting microchip. In this embodiment, at least one fluid discharge port and at least one fluid supply port are both arranged in a particle sorting microchip. For example, at least one fluid discharge port and a fluid storage container can be fluidically connected together, and can be fluidically connected together, for example, through a flow channel connecting member (e.g., a tube). The fluid (specifically, the fluid containing particles) passing through the first particle sorting section can be discharged from at least one fluid discharge port to the outside of the one particle sorting microchip, and then travel to the fluid storage container through the flow channel connecting member. In addition, the fluid storage container and at least one fluid supply port can be fluidically connected together, and can be fluidically connected together, for example, through a flow channel connecting member (e.g., a tube). The fluid (specifically, the fluid containing particles) leaving the fluid storage container returns to the one particle sorting microchip from at least one fluid supply port, and then travels to the second particle sorting section.

[0086] In the present technology, "fluidly connected" may mean that two objects to be connected (eg, a fluid discharge port and a fluid storage container and a fluid storage container and a fluid supply port) are connected together by a flow channel connecting member or the like so that the fluid does not leak.

[0087] In the present technology, "micro" means that at least a portion of the flow channel included in each particle sorting microchip has a size of the micron (μm) level (specifically, a cross-sectional size of the micron level). That is, in the present technology, a "microchip" refers to a chip including a micron-level flow channel (specifically, a chip including a flow channel with a cross-sectional size of the micron level). For example, according to the present technology, a chip including a particle sorting section can be referred to as a microchip, and the particle sorting section includes a flow channel with a cross-sectional size of the micron level. In the present technology, a microchip can be a microchip including, for example, the particle sorting section 107 described in "1. Related Technology" above. In the particle sorting section 107, the cross-section of the main channel 105 is, for example, rectangular, and in the particle sorting section 107, the width d of the main channel 105 can be, for example, 100μm to 500μm (specifically, 100μm to 300μm). The width of the branch channel 108 can be smaller than the width of the main channel 105. The orifice 120 is circular in cross section, and the diameter of the orifice 120 at the connection between the orifice 120 and the main flow channel 105 may be, for example, 10 to 60 μm (specifically 20 to 50 μm). These dimensions on the flow channel may be appropriately changed according to the size of the particles.

[0088] The connection of the flow channel can be achieved, for example, by a flow channel connecting member (e.g., a tube). The material of the tube can be appropriately selected by a person skilled in the art from the materials used in the technical field to which the present technology belongs. The tube can be, for example, a polyvinyl chloride (PVC) tube, a silicone tube, a polyetheretherketone (PEEK) tube, a polytetrafluoroethylene (PTFE) tube, or a thermoplastic elastomer tube, or multiple types of tubes can be connected together. The flow channel connecting member can also be used to perform the connection between at least one fluid discharge port and a fluid storage container and the connection between the fluid storage container and at least one fluid supply port.

[0089] The particle sorting flow channel unit of the present technology includes at least one fluid storage container, and the fluid storage container is arranged between two particle sorting parts. That is, the fluid storage container is arranged on the flow channel connecting the two particle sorting parts together. More specifically, the fluid storage container is configured so that the fluid discharged from at least one fluid discharge port can flow into and can store the fluid. The fluid storage container can be configured so that the fluid stored therein can be discharged to the outside of the container, and is configured so that the fluid discharged from the container flows to at least one fluid supply port.

[0090] The fluid storage container is configured so that the fluid storage capacity in the container changes according to the flow difference before and after the container. More specifically, the fluid storage container can suppress the influence of flow fluctuations in the flow channel upstream of the fluid storage container on the flow in the flow channel downstream of the fluid storage container, or suppress the influence of flow fluctuations in the flow channel downstream of the fluid storage container on the flow in the flow channel upstream of the fluid storage container. Thus, for example, the fluid storage container can suppress the influence of flow fluctuations in one of the first particle sorting section or the second particle sorting section on the other particle sorting section. The fluid storage container can be used to produce such a suppressive effect.

[0091] In the present technology, flow fluctuation means that the flow direction is constant but the flow rate changes. Flow fluctuation can be irregular or regular fluctuation. In the present technology, flow fluctuation can be flow fluctuation caused by particle sorting operation (more specifically, pulsating flow caused by the drive of a pump or pulsating flow caused by particle sorting treatment). That is, the fluid storage container can be used to reduce the influence of the pulsating flow of the fluid flowing through either the first particle sorting section or the second particle sorting section on the flow in the other particle sorting section.

[0092] In addition, the flow rate upstream and downstream of the container can be independently controlled by the fluid storage container. That is, the fluid storage container can be used to independently control the flow rate of the fluid flowing through the first particle sorting section and the flow rate of the fluid flowing through the second particle sorting section. For example, the fluid storage container can control the flow rate of the fluid flowing out of at least one fluid discharge port to be greater or less than the flow rate of the fluid entering at least one fluid supply port.

[0093] From the viewpoint of ease of manufacturing, the number of the fluid storage containers disposed between the two particle sorting sections is preferably one to five, more preferably one to three, even more preferably one or two, and particularly preferably one.

[0094] According to one embodiment of the present technology, a fluid storage container can be configured so that a liquid-air interface is formed in the container. The fluid storage container forming the liquid-air interface is suitable for suppressing the influence of flow fluctuations caused by the particle sorting operations in the two particle sorting sections. For example, a pulsating flow can be dispersed or absorbed by the fluid storage container forming the liquid-air interface. That is, the fluid storage container can be used as a component for dispersing or absorbing a pulsating flow.

[0095] For example, the fluid storage container may be configured to expand as the fluid storage capacity changes (increases). The fluid storage container may be configured to expand due to the structure of the fluid storage container, or may be configured to expand due to the material properties (particularly, elastic properties) of the fluid storage container.

[0096] According to one embodiment of the present technology, the fluid storage container itself may include a material that does not have elastic properties. In this embodiment, the fluid storage container may be configured to be expandable due to the structure of the container. In this embodiment, the fluid storage container may be configured, for example, to be in the form of a sheet when no fluid is stored, and to increase the internal volume of the fluid storage container when storing fluid (e.g., a plastic bag, an infusion bag, etc.).

[0097] According to another embodiment of the present technology, the fluid storage container may include a material having elastic properties (e.g., a rubber material, etc.). In this embodiment, the fluid storage container itself stretches (e.g., expands like a balloon) so that more fluid can be stored inside.

[0098] The fluid storage container may be pre-filled with a gas, such as air or an inert gas, such as nitrogen and argon. When the fluid is stored in the fluid storage container, the gas may be compressed.

[0099] The interior of the fluid storage container may be provided with a filter. The filter may, for example, prevent contamination from external air. For example, the filter may be a filter capable of communicating the gas pressure (e.g., air pressure) inside the fluid storage container with the external air. The filter may include a material that does not allow liquid to penetrate.

[0100] The fluid storage container can be configured so that the fluid (specifically, liquid) flowing into the container does not leak from the container. For example, the material forming the fluid storage container can be a material that can change the fluid storage capacity and retain the fluid as described above. Those skilled in the art can appropriately select the material. The container can be, for example, a plastic bag. The plastic bag can be, for example, a bag including polyethylene, polypropylene, polyvinyl chloride or ethylene vinyl acetate copolymer.

[0101] The fluid storage container can be configured to be able to store a fluid, the amount (volume) of which is greater than or equal to the value obtained by multiplying the absolute value of the flow difference before and after the fluid storage container by the time the fluid flows in the particle sorting flow channel unit. Therefore, while the particle sorting process is performed by the particle sorting flow channel unit of the present technology, the fluid storage container can be prevented from being damaged or broken. The flow difference before and after the fluid storage container can be more specifically the difference between the flow rate in the flow channel that fluidically connects at least one fluid discharge port to the fluid storage container and the flow rate in the flow channel that fluidly connects the fluid storage container to at least one fluid supply port. Those skilled in the art can appropriately select a fluid storage container for storing a certain amount of fluid in consideration of the difference and time.

[0102] The fluid storage container may be provided at any position on the flow path connecting the first particle sorting section and the second particle sorting section. The position where the fluid storage container is provided may be, for example, the following (a) or (b).

[0103] (a) According to one embodiment of the present technology, a particle sorting flow channel unit according to the present technology may include an upstream particle sorting microchip and a downstream particle sorting microchip, the upstream particle sorting microchip may be provided with a first particle sorting section and at least one fluid discharge port, the downstream particle sorting microchip may be provided with a second particle sorting section and at least one fluid supply port, and a fluid storage container may be provided on a flow channel that fluidically connects at least one fluid discharge port with at least one fluid supply port. More specifically, the fluid storage container may be provided at any position on the flow channel connecting the fluid discharge port, in which particles selected at the first particle sorting section are discharged from the upstream particle sorting microchip to the fluid supply port for supplying the fluid to the downstream particle sorting microchip.

[0104] This embodiment will be described in more detail below in "(2) First Example of First Embodiment (Microparticle Sorting Flow Channel Unit)".

[0105] (b) According to another embodiment of the present technology, a particle sorting flow channel unit according to the present technology may include an upstream particle sorting microchip provided with a first particle sorting section and a downstream particle sorting microchip provided with a second particle sorting section, and a fluid storage container may be provided in either of the two particle sorting microchips.

[0106] For example, the fluid storage container may be disposed on the flow path between the first particle sorting section and the fluid discharge port, in which the particles sorted at the particle sorting section are discharged from the upstream particle sorting microchip. In this embodiment, another fluid discharge port and a fluid supply port may be further disposed between the first particle sorting section and the fluid discharge port, and the another fluid discharge port and the fluid supply port may be fluidically connected to the fluid storage container.

[0107] This embodiment will be described in more detail below in "(3) Second example of first embodiment (microparticle sorting flow channel unit)".

[0108] Alternatively, the fluid storage container may be disposed on the flow path between the fluid supply port of the downstream microparticle sorting microchip and the second particle sorting section in the downstream microparticle sorting microchip. For example, in the case where the flow toward the particle sorting section in the downstream microparticle sorting microchip is a laminar flow including the sample liquid and the sheath liquid described below, the fluid storage container may be disposed on the flow path between the fluid supply port of the downstream microparticle sorting microchip and the merging section for merging the sample liquid and the sheath liquid.

[0109] According to another embodiment of the present technology, in addition to the discharge of the particles sorted at the first particle sorting section in the upstream particle sorting microchip from the microchip to the fluid discharge port for supplying the fluid to the fluid supply port in the downstream particle sorting microchip, the fluid storage container can be set at any position on the flow channel connecting the fluid discharge port (e.g., the waste liquid discharge port). Therefore, for example, in the case of performing a sorting process on the particles discharged from the waste liquid discharge port of the upstream particle sorting microchip in the second particle sorting section, the flow rates in the two microchips can be independently controlled.

[0110] The fluid storage container may include, for example, an inlet for fluid flowing from upstream into the container and an outlet for fluid in the container to flow downstream. For example, the fluid discharge port and the inlet may be fluidly connected together by a flow channel connection member (e.g., a tube), and the outlet and the fluid supply port may be fluidly connected together by a flow channel connection member (e.g., a tube).

[0111] Connectors known in the art can be used to connect the inlet to the tube. Connectors known in the art can also be used to connect the outlet to the tube. Those skilled in the art can appropriately select the type of connector according to the size of the tube and the size of the inlet.

[0112] The particle sorting microchip constituting the particle sorting flow channel unit of the present technology includes at least one particle sorting section (for example, one or two particle sorting sections, and specifically one particle sorting section). The particle sorting section may include, for example, a flow channel for supplying a fluid containing particles to the particle sorting section, a flow channel through which a fluid containing particles sorted in the particle sorting section flows, and a flow channel through which a fluid containing particles not sorted in the particle sorting section flows.

[0113] The particle sorting microchip can be preferably used to perform on-chip sorting. That is, the particle sorting section is provided in the particle sorting microchip. The flow channel for supplying the fluid containing particles to the particle sorting section, the flow channel through which the fluid containing particles sorted in the particle sorting section flows, and the flow channel through which the fluid containing particles not sorted in the particle sorting section flows are all provided in the particle sorting microchip.

[0114] According to a preferred embodiment, the fluid flowing through the flow channel that supplies the fluid containing microparticles to the particle sorting section can be a laminar flow, which includes a sample liquid containing microparticles and a sheath fluid surrounding the sample liquid. The laminar flow allows the microparticles to flow side by side in a row, which is suitable for microparticle sorting. For example, the microparticles flow side by side in a row, thereby making it easier to irradiate each microparticle with light, and whether the microparticles are to be sorted can be determined based on the scattered light and / or fluorescence generated by the light irradiation.

[0115] According to one embodiment of the present technology, a particle sorting section of a particle sorting microchip includes a main channel through which a fluid (specifically, a liquid) containing particles flows, a branch channel branching from the main channel, and a particle sorting channel coaxial with the main channel. Examples of particle sorting microchips including a particle sorting section include the particle sorting microchip described in "1. Related Technology" above. That is, according to one embodiment of the present technology, the particle sorting microchip may be the particle sorting microchip described in "1. Related Technology" above, and is used to perform on-chip sorting. The particle sorting section of the particle sorting microchip described in "1. Related Technology" above includes a main channel through which a fluid containing particles flows, a branch channel branching from the main channel, and a particle sorting channel coaxial with the main channel. The main channel and the particle sorting channel can be connected to each other via an orifice portion coaxial with the main channel. The particles to be recovered flow to the particle sorting channel through the orifice portion. Other particles flow to the branch channel. A more detailed description of the particle sorting section and the configuration other than the particle sorting section is as described in “1. Related Art” above, and this description also applies to the microparticle sorting microchip used in the present technology.

[0116] The microparticle sorting microchip used in the present technology may be a microparticle sorting microchip other than the microparticle sorting microchip described in "1. Related Art" above.

[0117] In the case where the particle sorting flow channel unit of the present technology includes two or more particle sorting microchips (for example, two particle sorting microchips of an upstream particle sorting microchip and a downstream particle sorting microchip), the configurations of the particle sorting microchips may be the same as or different from each other.

[0118] According to one embodiment of the present technology, the fluid discharge port of the upstream microparticle sorting microchip is connected to the fluid supply port of the downstream microparticle sorting microchip.

[0119] The fluid discharge port of the upstream microparticle sorting microchip may preferably be a fluid discharge port in which microparticles sorted at the particle sorting section of the upstream microparticle sorting microchip are discharged from the microchip.

[0120] The fluid supply port of the downstream microparticle sorting microchip may preferably be a fluid supply port that supplies a fluid containing microparticles to the particle sorting section of the downstream microparticle sorting microchip.

[0121] The fluid discharge port of the upstream microparticle sorting microchip is connected to the fluid supply port of the downstream microparticle sorting microchip in this manner, whereby the fluid containing microparticles sorted by the upstream microparticle sorting microchip can be further subjected to microparticle sorting processing in the downstream microparticle sorting microchip.

[0122] According to one embodiment of the present technology, a pump can be arranged between the fluid discharge port and the fluid supply port. The flow rate of the fluid introduced into at least one fluid supply port upstream of the second particle sorting section can be controlled by the pump. The pump is preferably used to supply the fluid to the downstream particle sorting microchip.

[0123] The pump can be specifically arranged on the flow channel connecting the fluid discharge port and the fluid supply port. The pump can be, but is not limited to, for example, a peristaltic pump (tubing pump), a roller pump, a syringe pump or a centrifugal pump. The pump can preferably be a peristaltic pump or a roller pump for more accurate flow control.

[0124] According to a preferred embodiment of the present technology, the pump can be arranged between the fluid discharge port and the fluid supply port. More specifically, the pump can be arranged between the fluid discharge port of the upstream particle sorting microchip and the fluid supply port of the downstream particle sorting microchip. In this embodiment, the fluid storage container can be arranged upstream of the pump.

[0125] The fluid storage container is disposed upstream of the pump, thereby reducing or eliminating the influence of flow fluctuations (eg, pulsating flow) occurring when the fluid is introduced into the downstream particle sorting microchip through the pump on the flow in the upstream particle sorting microchip.

[0126] According to one embodiment of the present technology, a fluid storage container can be used as a container for recovering particles sorted in an upstream particle sorting microchip. That is, in this embodiment, the container is used to independently control the flow rates in two particle sorting microchips, and to recover particles sorted in the upstream particle sorting microchip. By using a fluid storage container as a particle recovery container, it is not necessary to separately provide a particle recovery container in the particle sorting flow channel unit, and the configuration of the flow channel unit can be simplified.

[0127] According to another embodiment of the present technology, a particle recovery container for recovering particles sorted in an upstream particle sorting microchip may be disposed downstream of the fluid storage container. The volume of the fluid storage space in the particle recovery container may be constant.

[0128] In the present technology, microparticles can be appropriately selected by those skilled in the art. In the present technology, microparticles can include biological microparticles (e.g., cells, microorganisms, and liposomes) and synthetic microparticles (e.g., latex microparticles, gel microparticles, and industrial microparticles). Biological microparticles can include chromosomes, liposomes, mitochondria, organelles (organelles) of cells, etc. that constitute various cells. Cells can include animal cells (e.g., hematopoietic cells) and plant cells. Microorganisms can include bacteria (e.g., Escherichia coli), viruses (e.g., tobacco mosaic virus), fungi (e.g., yeast), etc. In addition, biological microparticles can also include biopolymers (e.g., nucleic acids, proteins, and complexes thereof). In addition, synthetic microparticles can be, for example, microparticles including organic or inorganic polymer materials or metals. Organic polymer materials can include polystyrene, styrene-divinylbenzene, polymethyl methacrylate, etc. Inorganic polymer materials can include glass, silicon dioxide, magnetic materials, etc. Metals can include gold colloids, aluminum, etc. The shape of the microparticles can be spherical, substantially spherical, or non-spherical. Those skilled in the art can appropriately select the size and mass of the microparticles according to the size of the flow channel of the microchip. On the other hand, the size of the flow channel of the microchip can also be appropriately selected according to the size and mass of the microparticles. In the present technology, chemical or biological markers (e.g., fluorescent dyes, etc.) can be attached to the microparticles as needed. The labels can facilitate the detection of the microparticles. Those skilled in the art can appropriately select the labels to be attached.

[0129] The fluid flowing through the particle sorting flow channel unit of the present technology is, for example, a liquid, a liquid substance or a gas, and is preferably a liquid. Those skilled in the art can appropriately select the type of fluid according to, for example, the type of particles to be sorted. For example, as the fluid, commercially available sample liquids and sheath fluids or sample liquids and sheath fluids known in the art can be used.

[0130] The particle sorting microchip constituting the particle sorting flow channel unit of the present technology can be manufactured by methods known in the art. For example, the particle sorting microchip can be manufactured, for example, by laminating two or more substrates on which a predetermined flow channel is formed. The flow channel can be formed on all of, for example, two or more substrates (specifically, two substrates), or can be formed on only a portion of two or more substrates (specifically, one of the two substrates). The flow channel is preferably formed on only one substrate so that the position can be more easily adjusted when the substrates are joined together.

[0131] As materials for forming the microchip for particle sorting, materials known in the art can be used. Examples include, but are not limited to, polycarbonate, cycloolefin polymer, polypropylene, polydimethylsiloxane (PDMS), polymethyl methacrylate (PMMA), polyethylene, polystyrene, glass, and silicone. Specifically, polymer materials (e.g., polycarbonate, cycloolefin polymer, and polypropylene) are particularly preferred because they have excellent processability and can manufacture microchips inexpensively by using molding equipment.

[0132] (2) First Example of the First Embodiment (Microparticle Sorting Flow Channel Unit)

[0133] According to one embodiment of the present technology, the particle sorting flow channel unit according to the present technology may include an upstream particle sorting microchip and a downstream particle sorting microchip, the upstream particle sorting microchip may be provided with a first particle sorting section and at least one fluid discharge port, the downstream particle sorting microchip may be provided with a second particle sorting section and at least one fluid supply port, and the fluid storage container may be provided on the flow channel that fluidically connects at least one fluid discharge port with at least one fluid supply port. Figure 4 An example of the microparticle sorting flow channel unit according to this embodiment is described. Figure 4 Schematic diagram of a particle sorting flow channel unit according to the present technology.

[0134] Figure 4 The particle sorting flow channel unit 400 shown is a fluid storage container added to Figure 3 The flow channel unit of the particle sorting flow channel unit shown in FIG. Figure 4 As shown, the particle sorting flow channel unit 400 includes two particle sorting microchips 100a and 100b, and these particle sorting microchips are connected together, for example, via a flow channel connecting member (e.g., a tube) 401. The particle sorting flow channel end 111a (i.e., a fluid discharge port) of the particle sorting microchip 100a is connected to one end of the flow channel connecting member 401, and the other end of the flow channel connecting member 401 is connected to the sample liquid inlet 101b (i.e., a fluid supply port) of the particle sorting microchip 100b. In addition, a pump 402 is provided upstream of the sample liquid inlet 101b, so as to introduce the sample liquid from the sample liquid inlet 101b into the particle sorting microchip 100b at a predetermined flow rate. The particle sorting microchip 100a is an upstream particle sorting microchip, and the particle sorting microchip 100b is a downstream particle sorting microchip.

[0135] In addition, a fluid storage container 403 is provided downstream of the particle sorting flow channel end 111a of the particle sorting microchip 100a and upstream of the pump 402. The fluid storage container 403 may include an inlet and an outlet, through which the liquid leaving the particle sorting microchip 100a from the particle sorting flow channel end 111a can flow in, and through which the fluid in the fluid storage container 403 can flow out.

[0136] The configuration of the particle sorting microchip 100a and the particle sorting microchip 100b is Figure 1 The configuration of the particle sorting microchip 100 shown is the same. Figure 1 The components shown in the drawings and indicated by specific reference numerals are Figure 4 The parts indicated by the reference numerals with a or b added thereto are identical. For example, Figure 4 The main flow channel 105a and the main flow channel 105b in Figure 1 Therefore, the description of each component of the microparticle sorting microchip 100a and the microparticle sorting microchip 100b will be omitted.

[0137] An example of a particle sorting operation using the particle sorting flow channel unit 400 will be described below.

[0138] The sample liquid and sheath liquid containing microparticles are introduced into the sample liquid flow channel 102a and the sheath liquid flow channel 104a from the sample liquid inlet 101a and the sheath liquid inlet 103a, respectively (hereinafter, the sample liquid and the sheath liquid introduced into the microparticle sorting microchip 100a are referred to as sample liquid a and sheath liquid a, respectively). The introduction of the sample liquid a and the sheath liquid a can be performed by a pump connected to the tubes of the sample liquid inlet 101a and the sheath liquid inlet 103a. The sample liquid a and the sheath liquid a merge at the merging portion 112a, and form a laminar flow in which the sample liquid a is surrounded by the sheath liquid a (hereinafter, the laminar flow in the microparticle sorting microchip 100a is referred to as laminar flow a). The laminar flow a flows to the particle sorting portion 107a through the main channel 105a.

[0139] In the detection area 106a provided in the main flow channel 105a, the microparticles in the sample liquid are irradiated with light. Based on the fluorescence and / or scattered light generated by the light irradiation, it is determined whether the microparticles are microparticles to be recovered. The determination can be made by whether the fluorescence and / or scattered light generated by the irradiation meets a first standard. The first standard can be preset by the user. The microparticles pass through the detection area 106a and flow to the particle sorting section 107a.

[0140] In the particle sorting section 107a, the laminar flow a is divided and flows to the two branch flow channels 108a. In addition, in the particle sorting section 107a, only in the case where the microparticles determined to be recovered flow, a flow entering the particle sorting flow channel 109a is formed, and the microparticles are recovered. In the microparticle sorting of the microparticle sorting microchip 100b, the liquid containing the recovered microparticles is used as the sample liquid (hereinafter, the sample liquid and the sheath liquid introduced into the microparticle sorting microchip 100b are referred to as the sample liquid b and the sheath liquid b, respectively).

[0141] The sample liquid b flows toward the particle sorting flow channel end 111a through the particle sorting flow channel 109a. The sample liquid b leaves the microparticle sorting microchip 100a at the particle sorting flow channel end 111a, and then flows toward the fluid storage container 403 through the flow channel connection member 401 connected at the particle sorting flow channel end 111a.

[0142] The pump 402 is provided upstream of the sample liquid inlet 101b and downstream of the fluid storage container 403. The sample liquid b is introduced into the sample liquid inlet 101b of the microparticle sorting microchip 100b by the pump 402. The sample liquid b is merged with the sheath liquid b introduced from the sheath liquid inlet 103b at the merging portion 112b, and a laminar flow is formed (hereinafter, the laminar flow in the microparticle sorting microchip 100b is referred to as laminar flow b). The laminar flow b flows to the particle sorting portion 107b through the main channel 105b.

[0143] In the detection area 106b arranged in the main flow channel 105b, the particles in the sample liquid are irradiated with light. Based on the fluorescence and / or scattered light generated by the light irradiation, it is determined whether the particles are particles to be recovered. The determination can be made by whether the fluorescence and / or scattered light generated by the irradiation meets the second standard. The second standard can be preset by the user. The second standard can be different from or the same as the first standard. The particles pass through the detection area 106b and flow to the particle sorting section 107b.

[0144] In the particle sorting section 107b, the laminar flow b is divided and flows to the two branch flow channels 108b. In addition, in the particle sorting section 107b, only when the microparticles determined to be recovered flow, the flow into the particle sorting flow channel 109b is formed, and the microparticles are recovered.

[0145] In the above particle sorting operation, there is a situation where the flow rate flowing through the particle sorting flow channel 109a does not match the flow rate of the sample liquid b introduced into the sample liquid inlet 101b by the pump 402. For example, the former may be greater than the latter, or the former may be less than the latter. In the case where these two flow rates do not match, the fluid storage capacity in the fluid storage container 403 changes according to the difference between the two flow rates. The fluid storage container 403 is configured so that the fluid storage capacity can be changed, thereby even under the condition that the two flow rates do not match, the particle sorting processing in each particle sorting microchip 100a and the particle sorting microchip 100b can be performed under flow conditions independent of each other.

[0146] In the case where the flow rate flowing through the particle sorting flow channel 109a is greater than the flow rate of the sample liquid b introduced into the sample liquid inlet 101b, the sample liquid b in an amount corresponding to the difference between the two flow rates flows into the fluid storage container 403, and the fluid storage capacity in the fluid storage container 403 increases with the inflow. Due to the increase in the fluid storage capacity, the fluid storage container 403 may expand, or the gas pre-filled in the fluid storage container 403 may be compressed. Due to the increase in the fluid storage capacity, the flow rate of the sample liquid b introduced into the sample liquid inlet 101b of the microparticle sorting microchip 100b is not affected by the flow rate flowing through the particle sorting flow channel 109a, but is the flow rate controlled by the pump 402.

[0147] In addition, when the sample liquid b is introduced into the microparticle sorting microchip 100b by the pump 402, the pump 402 can generate a pulsating flow. For example, a peristaltic pump can generate a pulsating flow. The fluid storage container 403 is arranged upstream of the pump 402, thereby suppressing the influence of the pulsating flow generated by the drive of the pump 402 on the flow in the flow channel connecting member (tube) 401 upstream of the fluid storage container 403, and further suppressing the influence on the flow in the microparticle sorting microchip 100a.

[0148] In the case where the flow rate flowing through the particle sorting flow channel 109a is smaller than the flow rate of the sample liquid b introduced into the sample liquid inlet 101b, an amount of liquid corresponding to the difference between the two flow rates flows out from the fluid storage container 403. In this case, for example, before the microparticle sorting flow channel unit 400 starts the microparticle sorting process, a predetermined amount of liquid may be contained in the fluid storage container 403. The liquid flows from the fluid storage container 403 to the flow channel connecting member (tube) 401 according to the difference between the above two flow rates. Therefore, the flow rate flowing through the particle sorting flow channel 109a is not affected by the flow rate of the sample liquid b introduced into the sample liquid inlet 101b of the microparticle sorting microchip 100b.

[0149] In addition, as described above, the fluid storage container 403 is arranged upstream of the pump 402, thereby suppressing the influence of the pulsating flow generated by the pump 402 on the flow in the flow channel connecting member (tube) 401 upstream of the fluid storage container 403, and further, suppressing the influence on the flow in the particle sorting microchip 100a.

[0150] As described above, the flow rates in the microparticle sorting microchip 100 a and the microparticle sorting microchip 100 b can be independently controlled by the fluid storage container 403 .

[0151] The fluid storage container 403 can be used as a container for recovering the particles sorted in the particle sorting microchip 100a. For example, in the case where the flow rate flowing through the particle sorting flow channel 109a is greater than the flow rate of the sample liquid b introduced into the sample liquid inlet 101b, the sample liquid b in an amount corresponding to the difference between the two flow rates flows into the fluid storage container 403. Therefore, the particles sorted in the particle sorting microchip 100a are recovered in the fluid storage container 403. Note that a part of the particles recovered in the fluid storage container 403 can be subjected to a particle sorting operation by the particle sorting microchip 100b through the pump 402. Therefore, for example, the particles recovered in the fluid storage container 403 can be compared with the particles recovered in the particle sorting flow channel 109b of the particle sorting microchip 100b. For example, in the case where the first standard and the second standard are different from each other, the proportion of particles satisfying the second standard in the particles satisfying the first standard can be known.

[0152] (3) Second Example of the First Embodiment (Microparticle Sorting Flow Channel Unit)

[0153] According to one embodiment of the present technology, the particle sorting flow channel unit according to the present technology includes an upstream particle sorting microchip provided with a first particle sorting section and a downstream particle sorting microchip provided with a second particle sorting section, and a fluid storage container can be provided on the flow channel between the first particle sorting section and a fluid discharge port, in which particles selected in the particle sorting section are discharged from the upstream particle sorting microchip. In this embodiment, another fluid discharge port and a fluid supply port can be further provided between the first particle sorting section and the fluid discharge port, and another fluid discharge port and a fluid supply port can be fluidically connected to the fluid storage container. The following will refer to Figure 5 An example of the microparticle sorting flow channel unit according to this embodiment is described. Figure 5 Schematic diagram of a particle sorting flow channel unit according to the present technology.

[0154] Figure 5 The particle sorting flow channel unit 500 shown is a fluid storage container added to Figure 3 The flow channel unit of the particle sorting flow channel unit shown in FIG. Figure 5As shown, the particle sorting flow channel unit 500 includes two particle sorting microchips 100a and 100b, and these particle sorting microchips are connected together, for example, via a flow channel connecting member (e.g., a tube) 501. The particle sorting flow channel end 111a (i.e., a fluid discharge port) of the particle sorting microchip 100a is connected to one end of the flow channel connecting member 501, and the other end of the flow channel connecting member 501 is connected to the sample liquid inlet 101b (i.e., a fluid supply port) of the particle sorting microchip 100b. In addition, a pump 502 is provided upstream of the sample liquid inlet 101b, so as to introduce the sample liquid from the sample liquid inlet 101b into the particle sorting microchip 100b at a predetermined flow rate. The particle sorting microchip 100a is an upstream particle sorting microchip, and the particle sorting microchip 100b is a downstream particle sorting microchip.

[0155] In addition, a fluid storage container 503 is provided on the particle sorting flow channel 109a of the particle sorting microchip 100a. That is, another fluid discharge port and another fluid supply port (not shown) are also provided between the particle sorting part and the fluid discharge port of the particle sorting microchip 100a, in which the particles selected in the particle sorting part are discharged from the microchip. The fluid storage container 503 is configured so that liquid can flow into the fluid storage container 503 through the another fluid discharge port, and is configured so that the liquid in the fluid storage container 503 is returned to the particle sorting flow channel 109a through the another fluid supply port.

[0156] The configuration of the particle sorting microchip 100a is similar to that of the microparticle sorting microchip 100a except that a fluid storage container 503 is added and another fluid discharge port and another fluid supply port are provided. Figure 1 The configuration of the particle sorting microchip 100 shown is the same.

[0157] Configuration of the particle sorting microchip 100b Figure 1 The configuration of the particle sorting microchip 100 shown is the same.

[0158] Each component of the particle sorting microchip 100a and the particle sorting microchip 100b is Figure 1 Corresponding to each component in. That is, Figure 1 The components shown in the drawings and indicated by specific reference numerals are Figure 5 Components indicated by reference numerals to which a or b is added are the same. Therefore, description of each component of the microparticle sorting microchip 100a and the microparticle sorting microchip 100b will be omitted.

[0159] An example of a particle sorting operation using the particle sorting flow channel unit 500 will be described below.

[0160] As described in "(2) First Example of the First Embodiment (Particle Sorting Flow Channel Unit)" above, particle sorting in the particle sorting microchip 100a is performed, and particles determined to be recovered are recovered in the particle sorting flow channel 109a. Liquid containing particles flows through the particle sorting flow channel 109a. This liquid is used as a sample liquid in the particle sorting of the particle sorting microchip 100b (hereinafter, the liquid flowing to the particle sorting flow channel end 111a through the particle sorting flow channel 109a is referred to as sample liquid b).

[0161] The sample liquid b leaves the microparticle sorting microchip 100a from the particle sorting flow channel end 111a, and further flows to the sample liquid inlet 101b of the microparticle sorting microchip 100b through the flow channel connecting member 501.

[0162] The pump 502 is arranged upstream of the sample liquid inlet 101b and downstream of the particle sorting flow channel end 111a. The sample liquid b is introduced into the sample liquid inlet 101b of the particle sorting microchip 100b by the pump 502. The sample liquid b merges with the sheath liquid b introduced from the sheath liquid inlet 103b at the merging section 112b, and forms a laminar flow (hereinafter, the laminar flow in the particle sorting microchip 100b is referred to as laminar flow b). The laminar flow b flows to the particle sorting section 107b through the main channel 105b. As described in the above "(2) First example of the first embodiment (particle sorting flow channel unit)", particle sorting is performed in the particle sorting section 107b, and the particles determined to be recovered are recovered in the particle sorting flow channel 109b.

[0163] In the above particle sorting operation, there is a situation where the flow rate flowing through the particle sorting flow channel 109a does not match the flow rate of the sample liquid b introduced into the sample liquid inlet 101b by the pump 502. For example, the former may be greater than the latter, or the former may be less than the latter. In the case where these two flow rates do not match, the fluid storage capacity in the fluid storage container 503 changes according to the difference between the two flow rates. The fluid storage container 503 is configured so that the fluid storage capacity can be changed, thereby even under the condition that the two flow rates do not match, the particle sorting operations in each particle sorting microchip 100a and the particle sorting microchip 100b can be performed under flow conditions independent of each other.

[0164] In the case where the flow rate flowing through the particle sorting flow channel 109a is greater than the flow rate of the sample liquid b introduced into the sample liquid inlet 101b, the sample liquid b in an amount corresponding to the difference between the two flow rates flows into the fluid storage container 503, and the fluid storage capacity in the fluid storage container 503 increases with the inflow. Due to the increase in the fluid storage capacity, the fluid storage container 503 may expand, or the gas pre-filled in the fluid storage container 503 may be compressed. Due to the increase in the fluid storage capacity, the flow rate of the sample liquid b introduced into the sample liquid inlet 101b of the microparticle sorting microchip 100b is not affected by the flow rate flowing through the particle sorting flow channel 109a, and is a flow rate controlled by the pump 502.

[0165] In addition, when the sample liquid b is introduced into the particle sorting microchip 100b by the pump 502, the pump 502 can generate a pulsating flow. For example, a peristaltic pump can generate a pulsating flow. The fluid storage container 503 is arranged upstream of the pump 502, thereby suppressing the influence of the pulsating flow generated by the drive of the pump 502 on the flow in the particle sorting flow channel 109a upstream of the fluid storage container 503, and further suppressing the influence on the flow in the flow channel further upstream in the particle sorting microchip 100a.

[0166] In the case where the flow rate flowing through the particle sorting flow channel 109a is smaller than the flow rate of the sample liquid b introduced into the sample liquid inlet 101b, an amount of liquid corresponding to the difference between the two flow rates flows out from the fluid storage container 503. In this case, for example, before the microparticle sorting flow channel unit 500 starts the microparticle sorting process, a predetermined amount of liquid may be contained in the fluid storage container 503. The liquid flows from the fluid storage container 503 into the particle sorting flow channel 109a downstream of the fluid storage container 503 according to the difference between the above two flow rates. Therefore, the flow rate in the particle sorting flow channel 109a upstream of the fluid storage container 503 is suppressed from being affected by the flow rate of the sample liquid b introduced into the sample liquid inlet 101b of the microparticle sorting microchip 100b.

[0167] In addition, as described above, the fluid storage container 503 is arranged upstream of the pump 502, thereby suppressing the influence of the pulsating flow generated by the pump 502 on the flow in the particle sorting channel 109a upstream of the fluid storage container 503, and further, suppressing the influence on the flow in the flow channel further upstream in the particle sorting microchip 100a.

[0168] As described above, the flow rates in the microparticle sorting microchip 100 a and the microparticle sorting microchip 100 b can be independently controlled by the fluid storage container 503 .

[0169] As described in connection with the container 403 in "(2) First Example of First Embodiment (Microparticle Sorting Flow Channel Unit)" above, the fluid storage container 503 can be used as a container for recovering microparticles sorted in the microparticle sorting microchip 100a.

[0170] (4) Third Example of the First Embodiment (Microparticle Sorting Flow Channel Unit)

[0171] According to one embodiment of the present technology, a particle recovery container for recovering the particles sorted in the first particle sorting microchip can be arranged downstream of the fluid storage container. In this embodiment, the volume of the fluid storage space in the particle recovery container can be constant. Figure 6 An example of the microparticle sorting flow channel unit according to this embodiment is described. Figure 6 Schematic diagram of a particle sorting flow channel unit according to the present technology.

[0172] Figure 6 The particle sorting flow channel unit 600 shown is a flow channel unit in which a fluid storage container is added to Figure 3 The particle sorting flow channel unit shown in FIG. 1 and the particle recovery container are further added downstream of the fluid storage container. Figure 6 As shown, the particle sorting flow channel unit 600 includes two particle sorting microchips 100a and 100b, and these particle sorting microchips are connected together, for example, via a flow channel connecting member (e.g., a tube) 601. The particle sorting flow channel end 111a (i.e., a fluid discharge port) of the particle sorting microchip 100a is connected to one end of the flow channel connecting member 601, and the other end of the flow channel connecting member 601 is connected to the sample liquid inlet 101b (i.e., a fluid supply port) of the particle sorting microchip 100b. In addition, a pump 602 is provided upstream of the sample liquid inlet 101b, so as to introduce the sample liquid from the sample liquid inlet 101b into the particle sorting microchip 100b at a predetermined flow rate. The particle sorting microchip 100a is an upstream particle sorting microchip, and the particle sorting microchip 100b is a downstream particle sorting microchip.

[0173] In addition, the fluid storage container 603 is arranged downstream of the particle sorting flow channel end 111a of the particle sorting microchip 100a and upstream of the pump 602. In addition, the particle recovery container 604 is arranged downstream of the fluid storage container 603 and upstream of the pump 602. That is, the fluid storage container 603 and the particle recovery container 604 downstream thereof are arranged between the particle sorting parts of the two sorting microchips 100a and 100b (that is, arranged on the flow channel connecting the two particle sorting parts together). The fluid storage container 603 and the particle recovery container 604 are configured so that liquid can flow in from the flow channel connecting the two particle sorting parts together.

[0174] The configuration of the particle sorting microchip 100a and the particle sorting microchip 100b is Figure 1 The configuration of the particle sorting microchip 100 shown is the same. Each component of the particle sorting microchip 100a and the particle sorting microchip 100b is the same as that of the particle sorting microchip 100a. Figure 1 Corresponding to each component in.

[0175] An example of a particle sorting operation using the particle sorting flow channel unit 600 will be described below.

[0176] As described in "(2) First Example of the First Embodiment (Particle Sorting Flow Channel Unit)" above, particle sorting in the particle sorting microchip 100a is performed, and particles determined to be recovered are recovered in the particle sorting flow channel 109a. Liquid containing particles flows through the particle sorting flow channel 109a. This liquid is used as a sample liquid in the particle sorting of the particle sorting microchip 100b (hereinafter, the liquid flowing to the particle sorting flow channel end 111a through the particle sorting flow channel 109a is referred to as sample liquid b).

[0177] The sample liquid b leaves the microparticle sorting microchip 100a from the particle sorting flow channel end 111a, and further flows to the sample liquid inlet 101b of the microparticle sorting microchip 100b through the flow channel connecting member 601.

[0178] The pump 602 is arranged upstream of the sample liquid inlet 101b and downstream of the particle sorting flow channel end 111a. The sample liquid b is introduced into the sample liquid inlet 101b of the particle sorting microchip 100b by the pump 602. The sample liquid b merges with the sheath liquid b introduced from the sheath liquid inlet 103b at the merging section 112b, and forms a laminar flow (hereinafter, the laminar flow in the particle sorting microchip 100b is referred to as laminar flow b). The laminar flow b flows to the particle sorting section 107b through the main channel 105b. As described in the above "(2) First example of the first embodiment (particle sorting flow channel unit)", particle sorting is performed in the particle sorting section 107b, and the particles determined to be recovered are recovered in the particle sorting flow channel 109b.

[0179] As described in “(2) First Example of First Embodiment (Particle Sorting Flow Channel Unit)” above, in the above particle sorting operation, the flow rates in the particle sorting microchip 100a and the particle sorting microchip 100b can be independently controlled by the fluid storage container 603 .

[0180] Furthermore, the particle recovery container 604 is disposed downstream of the fluid storage container 603. Therefore, the fluid storage container 603 does not need to be configured so that particles flowing into the inside can be taken out to the outside, and the particle recovery container 604 can be configured so that the volume inside the fluid storage space is constant (i.e., it does not need to be configured so that the difference between the flow rates of the two particle sorting microchips can be absorbed).

[0181] 3. Second embodiment (particle sorting device)

[0182] The particle sorting device of the present technology includes a particle sorting flow channel unit, which includes: a first particle sorting section; a fluid storage container located downstream of the first particle sorting section and capable of storing a fluid; and a second particle sorting section located downstream of the fluid storage container, wherein the fluid storage container is fluidically connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, and the fluid storage container is configured so that the fluid storage capacity in the container changes according to the flow rate difference before and after the container. Because the particle sorting flow channel unit is the particle sorting flow channel unit described in "2. First embodiment (particle sorting flow channel unit)" above, the description of the particle sorting flow channel unit is omitted.

[0183] The particle sorting device of the present technology can be a device that independently controls the flow rate of a fluid flowing through a first particle sorting section and the flow rate of a fluid flowing through a second particle sorting section. For example, using the particle sorting device of the present technology, from particles sorted according to the presence or absence of a specific characteristic in the first particle sorting section, particles can be further sorted according to the presence or absence of another characteristic in the second particle sorting section. In addition, the purity of target particles contained in the particles sorted in the first particle sorting section can be further improved in the second particle sorting section. The particle sorting device of the present technology can perform this two-step sorting continuously in one device.

[0184] The following will refer to Figure 7 An example of a microparticle sorting device according to the present technology is described.

[0185] The particle sorting device 700 includes the particle sorting flow channel unit 400. The particle sorting flow channel unit 400 is as described in "(2) First example of the first embodiment (particle sorting flow channel unit)" above.

[0186] The microparticle sorting device 700 may include a light irradiation unit 701a that irradiates microparticles flowing through the detection area 106a in the microparticle sorting microchip 100a with light and a detection unit 702a that detects scattered light and / or fluorescence generated by the light irradiation.

[0187] The microparticle sorting device 700 may further include a light irradiation unit 701b that irradiates microparticles flowing through the detection area 106b in the microparticle sorting microchip 100b with light and a detection unit 702b that detects scattered light and / or fluorescence generated by the light irradiation.

[0188] The microparticle sorting device 700 may include a control unit 703. The control unit 703 controls the sorting of microparticles based on information about light detected by the detection unit 702a in the microparticle sorting microchip 100a. In addition, the control unit 703 also controls the sorting of microparticles based on information about light detected by the detection unit 702b in the microparticle sorting microchip 100b.

[0189] Hereinafter, the light irradiation units 701 a and 701 b , the detection units 702 a and 702 b , and the control unit 703 will be described.

[0190] The light irradiation unit 701a irradiates the particles flowing through the detection area 106a in the particle sorting microchip with light (e.g., excitation light). The light irradiation unit 701a may include a light source that emits light and an objective lens that recovers the excitation light for the particles flowing through the detection area. The light source can be appropriately selected by a person skilled in the art according to the object of analysis, and may be, for example, a laser diode, an SHG laser, a solid-state laser, a gas laser, or a high-brightness LED, or a combination of two or more thereof. In addition to the light source and the objective lens, the light irradiation unit may include another optical element as needed. As described in "1. Related Art" above, the light irradiation unit 701a may, for example, be a unit that irradiates one position in the detection area with light or a unit that irradiates each of a plurality of positions with light. For example, the light irradiation unit 701a may irradiate each of two different positions in the detection area with light.

[0191] Similar to the light irradiation unit 701a, the light irradiation unit 701b also irradiates the microparticles flowing through the detection area 106b in the microparticle sorting microchip with light (for example, excitation light).

[0192] As described above, the microparticle sorting device of the present technology can include a first light irradiation unit for irradiating an upstream microparticle sorting microchip with light and a second light irradiation unit for irradiating a downstream microparticle sorting microchip with light. Therefore, microparticle sorting by two microparticle sorting microchips can be independently controlled.

[0193] The detection unit 702a detects scattered light and / or fluorescence generated from the microparticles by the irradiation of the light irradiation unit 701a. The detection unit 702a may include a condenser lens and a detector, and the condenser lens recovers the fluorescence and / or scattered light generated from the microparticles. As a detector, a PMT, a photodiode, a CCD, a CMOS, etc. can be used, but the detector is not limited to this. In addition to the condenser lens and the detector, the detection unit may include another optical element as needed. The detection unit may further include a spectroscopic unit, for example. Examples of optical components constituting the spectroscopic unit include gratings, prisms, and filters. The spectroscopic unit may, for example, detect light having a wavelength to be detected separately from light having another wavelength.

[0194] Similar to the detection unit 702a, the detection unit 702b also detects scattered light and / or fluorescence generated by light irradiation by the light irradiation unit 701b.

[0195] As described above, the particle sorting device of the present technology includes: a first detection unit that detects light generated by light irradiation of particles by the light irradiation unit of the upstream particle sorting microchip; and a second detection unit that detects light generated by light irradiation of particles by the light irradiation unit of the downstream particle sorting microchip. Therefore, the particle sorting of the two particle sorting microchips can be independently controlled.

[0196] The fluorescence detected by the detection unit 702a and the detection unit 702b may be, but is not limited to, the fluorescence generated by the microparticles themselves and the fluorescence generated by substances labeled on the microparticles (e.g., fluorescent substances, etc.). The scattered light detected by the detection unit may be forward scattered light, side scattered light, Rayleigh scattering, or Mie scattering, or a combination thereof.

[0197] The control unit 703 controls the sorting of the particles based on the data related to the light detected by the detection unit 702a. For example, in the case where the light detected by the detection unit 702a meets the predetermined standard, the control unit 703 can determine that the particles are to be sorted. From the light (fluorescence and / or scattered light) detected by the detection unit 702a, information related to the light can be generated. For example, information can be generated by converting light into an electrical signal. In order to generate information, the particle sorting device of the present technology may include an information generation unit that generates information related to the light from the light detected by the detection unit 702a. The information generation unit may be included in the control unit 703, or may be provided as a component separate from the control unit 703 in the particle sorting device, and not included in the control unit 703. The control unit 703 can determine whether the light detected by the detection unit 702a meets the predetermined standard based on the information related to the light. The control unit 703 can control the sorting of the particles based on the determined result.

[0198] Based on the determined result, in the case where the particles are particles to be recovered, the control unit 703 can change the flow in the flow channel so that the particles travel through the orifice into the particle sorting flow channel 109a. For example, the flow can be changed by reducing the pressure in the particle sorting flow channel 109a. In addition, after the particles are recovered, the control unit 703 can change the flow in the flow channel again. The flow can be changed again by increasing the pressure in the particle sorting flow channel. That is, the control unit 703 can be a unit that controls the pressure in the particle sorting flow channel based on information related to the light detected by the detection unit 702a.

[0199] For example, the control unit 703 may be a control unit having a function similar to that of the driving unit described in Japanese Patent Application Publication No. 2014-036604. That is, the control unit 703 may control an actuator configured to generate a negative pressure in the particle sorting flow channel 109a. In the case where it is determined based on information related to light that particles are to be recovered, the control unit 703 drives the actuator to generate a negative pressure in the particle sorting flow channel 109a. Therefore, the particles to be recovered are recovered in the particle sorting flow channel 109a. In the case where it is determined based on information related to light that particles are not to be recovered, the control unit 703 does not drive the actuator. Therefore, the particles that are not recovered flow to the branch flow channel 108a.

[0200] The actuator can be, for example, a piezoelectric element (e.g., a piezoelectric element). When it is determined that the particles are to be recovered, the control unit applies a voltage to the piezoelectric element that causes piezoelectric contraction to increase the volume in the particle sorting flow channel 109a. Due to the increase in volume, a negative pressure is generated in the particle sorting flow channel 109a. Therefore, a flow from the main flow channel to the particle sorting flow channel is formed, and the particles are recovered in the particle sorting flow channel 109a. When it is determined that the particles are not to be recovered, no voltage is applied. Therefore, a flow to the particle sorting flow channel 109a is not formed, and the particles flow to the branch flow channel 108a.

[0201] The control unit 703 also controls sorting of microparticles based on data related to light detected by the detection unit 702b. The control can be performed similarly to the control of sorting of microparticles based on data related to light detected by the detection unit 702a.

[0202] Example

[0203] 4. Examples

[0204] Preparation with Figure 8The particle sorting flow channel unit 800 of the configuration shown. The particle sorting flow channel unit 800 includes an upstream particle sorting microchip 900a and a downstream particle sorting microchip 900b. These particle sorting microchips are microchips having a configuration similar to that of the particle sorting microchip 100a and the particle sorting microchip 100b described in "(2) First Example of the First Embodiment (Particle Sorting Flow Channel Unit)" above.

[0205] The microparticle sorting microchip 900a and the microparticle sorting microchip 900b are connected together via a flow channel connecting member (comprising various types of tubes) 801. The particle sorting flow channel end 911a of the microparticle sorting microchip 900a is connected to one end of the flow channel connecting member 801, and the other end of the flow channel connecting member 801 is connected to the sample liquid inlet 901b of the microparticle sorting microchip 900b. In the flow channel 801, Figure 8 Segments a, c, d, and g shown are PEEK tubing with an outer diameter of 1 / 32" and an inner diameter of 0.25 mm. Segment b is PVC tubing with an outer diameter of 2.1 mm and an inner diameter of 0.25 mm. Segments e and f are tubing with an outer diameter of 3.68 mm and an inner diameter of 0.51 mm (PharMed BPT).

[0206] The pump 802 is provided upstream of the sample liquid inlet 901b so as to introduce the sample liquid from the sample liquid inlet 901b into the microparticle sorting microchip 900b at a predetermined flow rate. The pump 802 is a peristaltic pump.

[0207] In addition, a fluid storage container 803 is provided downstream of the particle sorting flow channel end 911a of the particle sorting microchip 900a and upstream of the pump 802. That is, the fluid storage container 803 is located downstream of the first particle sorting section 107a and is provided upstream of the second particle sorting section 107b. The fluid storage container 803 is a PE film bag that can expand up to 140 ml in volume.

[0208] The flow measurement device 804 and the flow measurement device 805 are respectively disposed upstream and downstream of the fluid storage container 803. The flow measurement device 804 and the flow measurement device 805 are both SLI-1000 (manufactured by Sensirion AG).

[0209] Distilled water was allowed to flow into the upstream microparticle sorting microchip 900a and the downstream microparticle sorting microchip 900b under the following conditions.

[0210] <Upstream Particle Sorting Microchip 900a>

[0211] Pressure of liquid introduced from sheath liquid inlet 103a: 120 kPa

[0212] Pressure of liquid introduced from gate inlet 121a: 130 kPa

[0213] Flow rate of liquid introduced into sample liquid inlet 901a: 100 μl / min

[0214] Back pressure at branch channel end 110a: atmospheric pressure

[0215] Flow rate through the particle sorting flow channel 109a: measured by the flow measurement device 804

[0216] The suction operation is not performed on the particle sorting flow channel 109a. That is, the liquid introduced from the gate inlet 121a flows from the particle sorting flow channel 109a to the downstream flow channel.

[0217] <Downstream Particle Sorting Microchip 900b>

[0218] Pressure of liquid introduced from sheath liquid inlet 103b: 120 kPa

[0219] Pressure of liquid introduced from gate inlet 121b: 130 kPa

[0220] Flow rate of the liquid introduced into the sample liquid inlet 901b: measured by the flow measurement device 805

[0221] Back pressure at branch channel end 110b: atmospheric pressure

[0222] Back pressure at particle separation channel end 911b: atmospheric pressure

[0223] Flow rate through particle sorting channel 109b: 260 μl / min

[0224] The suction operation is not performed on the particle sorting flow channel 109b.

[0225] Fig. 9 and Fig.10 FIG. 8 shows the flow rates measured by the flow measuring device 804 and the flow measuring device 805 when distilled water is allowed to flow under the above conditions. Fig.10 As shown in FIG. 8 , a pulsating flow is measured by the flow measuring device 805. That is, a pulsating flow is generated by the pump 802. Fig. 9 As shown, the flow rate measured by the flow measurement device 804 is constant. Therefore, it can be seen that the pulsating flow generated by the driving of the pump 802 does not affect the flow rate upstream of the fluid storage container 803.

[0226] In addition, if Fig. 9 As shown, the flow rate measured by the flow measurement device 804 is about 260 μl / min, while Fig.10As shown, the flow rate measured by the flow measurement device 805 is about 70 μl / min (excluding the time period when the pulsating flow is generated). That is, the upstream flow rate and the downstream flow rate of the fluid storage container 803 are significantly different from each other. Despite such a difference in flow rate, the flow rate of the liquid introduced into the sample liquid inlet 901b of the particle sorting microchip 900b is still controlled by the pump 802. Therefore, it can be seen that the flow rate in the upstream particle sorting microchip 900a (specifically, the flow rate flowing through the particle sorting flow channel 109a) and the flow rate in the downstream particle sorting microchip 900b (specifically, the flow rate of the liquid introduced into the sample liquid inlet 901b) can be independently controlled by the fluid storage container 803.

[0227] In the above particle sorting operation, the particle sorting flow channels in the particle sorting microchip 900a and the particle sorting microchip 900b were not pumped. However, the flow fluctuation due to the pumping was very small. Therefore, it is clear that the pumping in one particle sorting microchip does not affect the flow in the flow channel of the other particle sorting microchip.

[0228] Note that the present technology may also have the following configurations.

[0229] [1] A particle sorting flow channel unit, comprising:

[0230] a first particle sorting section;

[0231] a fluid storage container located downstream of the first particle sorting section and capable of storing a fluid; and

[0232] The second particle sorting section is located downstream of the fluid storage container, wherein

[0233] The fluid storage container is fluidly connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, and

[0234] The fluid storage container is configured so that the fluid storage capacity in the container changes according to the flow rate difference before and after the container.

[0235] [2] A particle sorting flow channel unit according to [1], wherein the fluid storage container suppresses the influence of flow fluctuations in the flow channel upstream or downstream of the fluid storage container on the flow in the flow channel downstream or upstream of the fluid storage container.

[0236] [3] The particle sorting flow channel unit according to [1] or [2], wherein:

[0237] The particle sorting flow channel unit includes a first particle sorting microchip and a second particle sorting microchip, and

[0238] The first particle sorting section is provided in the first microparticle sorting microchip, and the second particle sorting section is provided in the second microparticle sorting microchip.

[0239] [4] The particle sorting flow channel unit according to any one of [1] to [3], wherein:

[0240] The pump is disposed between the fluid discharge port and the fluid supply port, and

[0241] A fluid storage container is disposed upstream of the pump.

[0242] [5] The particle sorting flow channel unit according to any one of [1] to [4], wherein the fluid storage container is used to independently control the flow rate of the fluid flowing through the first particle sorting section and the flow rate of the fluid flowing through the second particle sorting section.

[0243] [6] A particle sorting flow channel unit according to any one of [1] to [5], wherein the fluid storage container is used to reduce the influence of the pulsating flow of the fluid flowing through either the first particle sorting section or the second particle sorting section on the flow in the other particle sorting section.

[0244] [7] The particle sorting flow channel unit according to any one of [1] to [6], wherein:

[0245] The particle sorting flow channel unit includes an upstream particle sorting microchip and a downstream particle sorting microchip.

[0246] The upstream particle sorting microchip is provided with a first particle sorting section and at least one fluid discharge port,

[0247] The downstream particle sorting microchip is provided with a second particle sorting section and at least one fluid supply port, and

[0248] The fluid storage container is disposed on a flow path that fluidly connects the at least one fluid discharge port and the at least one fluid supply port.

[0249] [8] The microparticle sorting flow channel unit according to any one of [1] to [7], wherein the fluid storage container is used as a container for recovering microparticles sorted in the first particle sorting section.

[0250] [9] The particle sorting flow channel unit according to any one of [1] to [8], wherein a particle recovery container for recovering particles sorted in the first particle sorting section is provided downstream of the fluid storage container.

[0251]

[10] The particle sorting flow channel unit according to [9], wherein the volume of the fluid storage space in the particle recovery container is constant.

[0252]

[11] The particle sorting flow channel unit according to any one of [1] to [6], wherein:

[0253] The particle sorting flow channel unit includes an upstream particle sorting microchip provided with a first particle sorting section and a downstream particle sorting microchip provided with a second particle sorting section, and

[0254] The fluid storage container is disposed in either of the two particle sorting microchips.

[0255]

[12] The particle sorting flow channel unit according to any one of [1] to

[11] , wherein:

[0256] At least one of the first particle sorting section and the second particle sorting section comprises:

[0257] a main flow channel through which the fluid containing the particles flows,

[0258] tributaries, branches from the main channel, and

[0259] The particle separation channel is coaxial with the main channel.

[0260]

[13] A particle sorting flow channel unit according to any one of [1] to

[12] , wherein the fluid storage container is configured to be able to store a fluid whose amount is greater than or equal to a value obtained by multiplying the absolute value of the flow rate difference before and after the container by the time the fluid flows in the particle sorting flow channel unit.

[0261]

[14] A particle sorting device, comprising a particle sorting flow channel unit, the particle sorting flow channel unit comprising:

[0262] a first particle sorting section;

[0263] a fluid storage container located downstream of the first particle sorting section and capable of storing a fluid; and

[0264] The second particle sorting section is located downstream of the fluid storage container, wherein

[0265] The fluid storage container is fluidly connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, and

[0266] The fluid storage container is configured so that the fluid storage capacity in the container changes according to the flow rate difference before and after the container.

[0267]

[15] The particle sorting device according to

[14] , wherein a flow rate of the fluid flowing through the first particle sorting section and a flow rate of the fluid flowing through the second particle sorting section are independently controlled.

[0268] Reference numerals list

[0269] 400 Particle Sorting Channel Unit

[0270] 401 Flow channel connection components

[0271] 402 Pump

[0272] 403 Fluid Storage Container

[0273] 100a, 100b Microparticle sorting microchip

[0274] 107a, 107b particle sorting section.

Claims

1. A particle sorting flow channel unit, comprising: a first particle sorting section; a fluid storage container, located downstream of the first particle sorting section and capable of storing a fluid; as well as The second particle sorting section is located downstream of the fluid storage container, wherein: The fluid storage container is fluidically connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, wherein the fluid connection means that two objects to be connected are connected together through a flow channel connection member so that the fluid does not leak, and The fluid storage container is configured to expand as the fluid storage capacity changes, A pump is disposed between the fluid discharge port and the fluid supply port, and the fluid storage container is disposed upstream of the pump.

2. The particle sorting flow channel unit according to claim 1, wherein: The fluid storage container suppresses the influence of flow rate fluctuation in the flow channel upstream or downstream of the fluid storage container on the flow rate in the flow channel downstream or upstream of the fluid storage container.

3. The particle sorting flow channel unit according to claim 1, wherein: The particle sorting flow channel unit includes a first particle sorting microchip and a second particle sorting microchip, and The first particle sorting section is provided in the first microparticle sorting microchip, and the second particle sorting section is provided in the second microparticle sorting microchip.

4. The particle sorting flow channel unit according to claim 1, wherein: The fluid storage container is used to independently control the flow rate of the fluid flowing through the first particle sorting section and the flow rate of the fluid flowing through the second particle sorting section.

5. The particle sorting flow channel unit according to claim 1, wherein: The fluid storage container is used to reduce the influence of the pulsating flow of the fluid flowing through any one of the first particle sorting section and the second particle sorting section on the flow rate in the other particle sorting section.

6. The particle sorting flow channel unit according to claim 1, wherein: The particle sorting flow channel unit includes an upstream particle sorting microchip and a downstream particle sorting microchip, The upstream particle sorting microchip is provided with the first particle sorting section and at least one fluid discharge port, The downstream particle sorting microchip is provided with the second particle sorting section and at least one of the fluid supply ports, and The fluid storage container is disposed on a flow passage that fluidly connects at least one of the fluid discharge ports and at least one of the fluid supply ports.

7. The particle sorting flow channel unit according to claim 1, wherein: The fluid storage container is used as a container for recovering the microparticles sorted in the first particle sorting section.

8. The particle sorting flow channel unit according to claim 1, wherein: A particle recovery container for recovering particles sorted in the first particle sorting section is provided downstream of the fluid storage container.

9. The particle sorting flow channel unit according to claim 8, wherein: The volume of the fluid storage space in the particle recovery container is constant.

10. The particle sorting flow channel unit according to claim 1, wherein: The particle sorting flow channel unit includes an upstream particle sorting microchip provided with the first particle sorting section and a downstream particle sorting microchip provided with the second particle sorting section, and The fluid storage container is disposed in any one of the two particle sorting microchips.

11. The particle sorting flow channel unit according to claim 1, wherein: At least one of the first particle sorting section and the second particle sorting section comprises: a main flow channel through which a fluid containing particles flows, a branch channel branching from the main channel, and The particle separation channel is coaxial with the main channel.

12. The particle sorting flow channel unit according to claim 1, wherein: The fluid storage container is configured to be able to store a fluid in an amount greater than or equal to a value obtained by multiplying an absolute value of a flow rate difference before and after the fluid storage container by a time for which the fluid flows in the particle sorting flow channel unit.

13. A particle sorting device, comprising a particle sorting flow channel unit, wherein the particle sorting flow channel unit comprises: a first particle sorting section; a fluid storage container, located downstream of the first particle sorting section and capable of storing a fluid; as well as The second particle sorting section is located downstream of the fluid storage container, wherein: The fluid storage container is fluidically connected to at least one fluid discharge port located downstream of the first particle sorting section and at least one fluid supply port located upstream of the second particle sorting section, wherein the fluid connection means that two objects to be connected are connected together through a flow channel connection member so that the fluid does not leak, and The fluid storage container is configured to expand as the fluid storage capacity changes, A pump is disposed between the fluid discharge port and the fluid supply port, and the fluid storage container is disposed upstream of the pump.

14. The particle sorting device according to claim 13, wherein: The flow rate of the fluid flowing through the first particle sorting section and the flow rate of the fluid flowing through the second particle sorting section are independently controlled.

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