WO2017103967A1 - Droplet forming device, droplet forming method, and liquid treatment system - Google Patents

Abstract

The purpose of the present invention is to provide a technology of forming droplets having a uniform droplet diameter, in the cases of forming droplets using centrifugal force. In order to achieve the purpose, this droplet forming device has: a liquid storing section for storing a first liquid; a first flow channel, which is connected to an outlet of the liquid storing section, and in which the first liquid flows; and a second flow channel, in which a second liquid different from the first liquid flows. The first flow channel and the second flow channel are connected to each other at a flow channel connecting area. Furthermore, the length of the first flow channel is configured to be longer than the straight-line distance from the outlet of the liquid storing section to the flow channel connecting area.

Description

Droplet generating apparatus, droplet generating method, and liquid processing system

The present invention relates to a droplet generation device, a droplet generation method, and a liquid processing system.

For example, when performing processing such as fluorescence analysis after nucleic acid amplification by the PCR method or the like, droplets are generated from the target solution, and the droplets are treated. Such a technique for droplet generation (droplet generation device) is disclosed in, for example, Patent Document 1. More specifically, Patent Document 1 is a droplet manufacturing device that includes an outer tube and an inner tube that is disposed inside the outer tube and that supplies a liquid droplet material. The inner tube discharge port is opened at the distal end portion of the inner tube formed on the downstream side, and the outer tube discharge port is opened at the distal end portion of the outer tube that is also formed on the downstream side in the fluid feeding direction. A droplet production device is disclosed in which a gap is formed between the inner tubes.

WO2015 / 137380 A1

When generating a droplet, for example, the droplet generation disk on which the droplet generation device is formed is rotated, and the solution to be processed is mixed with another liquid (for example, oil) using centrifugal force. Is generated.

However, when the droplet production device described in Patent Document 1 is used to generate droplets by centrifugal force, it takes time until the rotational speed of the disk is stabilized and the centrifugal force is stabilized, so the centrifugal force is stable. The droplets generated in the time until the end of the droplets have different droplet diameters compared to the droplets generated after the centrifugal force is stabilized. As a result, variation in droplet diameter when the entire droplet is considered becomes large, and it becomes difficult to obtain droplets with uniform droplet diameters.

The present invention has been made in view of such a situation, and provides a technique for generating droplets having a uniform droplet diameter when droplets are generated using centrifugal force.

In order to solve the above problems, a droplet generation device according to the present invention is a droplet generation device that generates droplets by using centrifugal force generated by rotating a disk, and contains a first liquid. It has a liquid storage part, a first flow path connected to the outlet of the liquid storage part, through which the first liquid flows, and a second flow path through which a second liquid different from the first liquid flows. And the 1st channel and the 2nd channel are connected in a channel connection location. Further, the length of the first flow path is configured to be longer than the linear distance from the outlet of the liquid storage portion to the flow path connection location.

Further features related to the present invention will become apparent from the description of the present specification and the accompanying drawings. The embodiments of the present invention are achieved and realized by elements and combinations of various elements and the following detailed description and appended claims.

It should be understood that the descriptions in this specification are merely exemplary, and are not intended to limit the scope of the invention or the application examples in any way.

According to the present invention, when droplets are generated using centrifugal force, droplets having a uniform droplet diameter can be generated.

It is a figure which shows the principal part structure of the droplet production | generation apparatus which concerns on the 1st Embodiment of this invention. In the embodiment of the present invention, it is a graph which shows the relation between time taken to produce a droplet, and channel length. It is a process figure for demonstrating the example of a droplet generation processing procedure concerning an embodiment of the present invention. It is a figure which shows the structural example of the liquid processing system which concerns on embodiment of this invention. It is a figure which shows the principal part structure of the droplet production | generation apparatus which concerns on the 2nd Embodiment of this invention.

One of the challenges of droplet generation using centrifugal force is that it takes a rise time from a stationary time until the rotational speed is stable and the centrifugal force becomes constant, and the size of the droplet generated during the rise time is the centrifugal force. Is different from the size of the droplets that are generated after that becomes constant, the variation in the droplet size as a whole increases.

In order to solve this problem, in the embodiment of the present invention, the length of the first liquid (solution) channel is set so that the first liquid channel and the second liquid channel are connected from the outlet of the first liquid container. It is set to be longer than the straight line distance to the place (droplet generation place). That is, for example, the first liquid flow path is meandered.

Hereinafter, embodiments of the present invention will be described with reference to the accompanying drawings. In the accompanying drawings, functionally identical elements may be denoted by the same numbers. The attached drawings show specific embodiments and implementation examples based on the principle of the present invention, but these are for understanding the present invention and are not intended to limit the present invention. Not used.

This embodiment has been described in sufficient detail for those skilled in the art to practice the present invention, but other implementations and configurations are possible without departing from the scope and spirit of the technical idea of the present invention. It is necessary to understand that the configuration and structure can be changed and various elements can be replaced. Therefore, the following description should not be interpreted as being limited to this.

(1) First Embodiment <Basic Configuration of Device>
FIG. 1 is a diagram showing a basic configuration of a main part of a droplet generating apparatus according to an embodiment of the present invention. FIG. 1 shows the minimum necessary configuration (basic unit device) of one unit formed on the droplet generation disk 101 of the droplet generation apparatus. Actually, one or more such basic unit devices are arranged on the droplet generating disk 101 having the rotation center 110.

The basic unit of the droplet generating device is a container 102 for storing an aqueous solution that is a raw material for generating a target droplet, a channel (solution channel) 103 extending from the container (aqueous solution container) 102, and a droplet. Container (oil container) 104 for storing the liquid (oil) outside, a flow path (oil flow path) 105 and 106 extending from the container 104, and a flow path (droplet) through which the generated liquid droplet passes. Channel) 108 and a droplet collection container 109 for collecting the produced droplets. The droplet generation disc 101 is detachable from the droplet generation device. Further, the droplet generation device has a centrifugal mechanism (not shown). In FIG. 1, two oil flow paths are provided, but one may be used. Each flow path is realized by carving a droplet generation disk (flat plate) 101 made of, for example, resin, glass, silicon, or the like, and capping with a similar material.

The container 102 and the container 104 are disposed closer to the rotation center 110 of the droplet generation disk 101 than the droplet recovery container 109. That is, the containers 102 and 104 are disposed on the inner peripheral side of the droplet generation disk 101, and the droplet recovery container 109 is disposed on the outer peripheral side of the droplet generation disk 101.

The container 102 is connected to the flow path 103 from the container outlet 111. The container 104 is connected to the flow paths 105 and 106 from the container outlets 112 and 113, respectively. The flow paths 105 and 106 are connected to the flow path 103 by a flow path connection portion 107. The flow paths 103, 105, and 106 are connected to the droplet recovery container 109 from the flow path connection portion 107 via the flow path 108.

Droplet generation is performed as follows. That is, the solution pushed out from the flow path 103 by the centrifugal force extends from the flow path connection portion 107 and is cut. The solution pushed out from the flow path connecting portion 107 is similarly mixed with the oil pushed out from the flow paths 105 and 106 by centrifugal force, and becomes spherical in the oil. Such a droplet operation is performed at the flow path connecting portion 107. Note that the diameter of the generated liquid droplet is approximately equal to the width (diameter) of the flow path 103 in the flow path connection portion 107.

In the basic unit of the droplet generating apparatus having each component as described above, the length of the flow path (solution flow path) 103 is longer than the linear distance between the container outlet 111 and the flow path connection portion 107. Yes. FIG. 1 shows a meandering flow path configuration as an example of the flow path 103. Although it is desirable that a part of the flow path 103 is not located on the inner peripheral side of the droplet generation disk 101 with respect to the container outlet 111, there is basically no restriction on how the flow path 103 is meandered. In this way, by adopting a curved shape instead of a straight line as in the prior art, the time required for the solution as a raw material for droplet generation to pass through the flow path 103 is increased, and the flow path 103 flows within the rise time. It is possible to delay the time for reaching the path connection unit 107 and forming droplets, and to reduce variations in droplet size. In FIG. 1, the flow path 103 is arranged on a plane by disposing it on a droplet generation disk (rotating disk) 101, but it may be meandered three-dimensionally. For example, a spiral configuration is easy to implement.

<Consideration of Effect of Droplet Generation by this Embodiment>
Here, the effect of droplet generation according to the present embodiment will be described with reference to each numerical formula and FIG.

In general, the relationship between the flow rate of the solution flowing inside the flow path and the differential pressure is expressed by Equation 1. Equation 1 is called Hagen-Poiseuille's relational expression. Here, Q is the volume flow rate, π is the circumference ratio, r is the radius of the flow path, ΔP is the pressure difference (differential pressure) between the container 102 and the droplet recovery container 109, μ is the viscosity of the liquid, and L1 is the flow rate. The length of the road.
Q = πr ⁴ × ΔP / (8 μ × L1) (Formula 1)

Further, the differential pressure ΔP is generated by centrifugal force and is proportional to the square of the angular velocity and the radius of rotation, and therefore can be expressed as Equation 2. Here, ρ is the density of the solution, L2 is the effective length of the flow path in the direction of the centrifugal force, in FIG. 1, the linear distance between the container outlet 111 and the connecting portion 107, ω is the angular velocity of rotation, and R is the radius of rotation. It is.
ΔP = ρ × L2 × πr ² × a / πr ² = ρ × L2 × R × ω ² (Expression 2)

Expression of volumetric flow rate excluding expression of differential pressure ΔP from Expression 1 and Expression 2 can be derived as Expression 3.
^{Q = (πr 4 / 8μ ×} L1) × ρ × L2 × R × ω 2
= (Πr ⁴ × R / (8 μ / ρ)) × (L2 / L1) × ω ² (Equation 3)
Here, if the number of rotations is fixed, the passage time (time required for droplet generation) t in which all the solution in the flow path 103 is lost is obtained by volume / deposition flow rate. Can be expressed.
t = (πr ² × L1) / Q
= ((8μ / ρ) / r ² × R) × (L1 ² / L2) × (1 / ω ² ) (Formula 4)

From Equation 4, it can be seen that the passage time t is proportional to the square of L1.

In order not to generate droplets during the rise time, it is sufficient that the time t is longer than the rise time.

FIG. 2 is a graph calculated by inputting a typical value for the relationship between the passage time t and L1. Here, L1 is represented by L2 (fixed length) and standardized (L1 / L2). In the graph, as shown in Equation 4, the passage time t increases rapidly in the shape of a parabola. The rise time of rotation varies depending on the type of centrifuge, but it takes 0.3 to several tens of seconds. Therefore, it is better that the ratio of L1 / L2 is long. In particular, it can be seen from the graph that L1 / L2 is preferably 2 or more in order to suppress variation in droplet size.

<Details of droplet generation process>
FIG. 3 is a process diagram for explaining a procedure of a droplet generation process that suppresses variation in droplet size.

(I) Step 301
The operator introduces a solution different from the raw material of the droplet (the aqueous solution stored in the container 102) into the channel 103.

Since the droplets generated at the rotation rise time of the droplet generation disk 101 are derived from the solution introduced into the flow path 103, a solution different from the raw material of the droplets is introduced, and then the droplets are generated by centrifugation. It is important to do. Since it is not preferable that droplets of the raw material are generated because the rotation speed of the droplet generation disk 101 is stabilized, a liquid different from the solution stored in the container 102 is introduced into the flow path 103. Until the rotation speed of the droplet generation disk 101 is stabilized (until the centrifugal force due to rotation is stabilized), liquid droplets introduced into the flow path 103 are generated. Since the droplets have different characteristics from the solution stored in the container 102, they can be distinguished later even if the sizes vary.

Specifically, oil used for droplet generation (the same as that contained in the container 104) is introduced into the channel 103. By doing in this way, the droplet of the solution used as a process target at the time of start-up can be prevented from being generated. Further, an aqueous solution containing a dye or a fluorescent material having a color different from the color of the aqueous solution used as a raw material for droplet generation may be introduced into the flow path 103. This makes it possible to discriminate droplets generated within the rise time in droplet measurement after droplet generation and exclude them from the droplet data to be analyzed. Can be small.

Note that the flow path 103 may be empty. However, in the case of air, since the resistance is small, it may be discharged immediately after the droplet generation disk 101 rotates, and it may not be possible to earn time until the centrifugal force is stabilized. It is preferable that a solution (oil or an aqueous solution having a different color) is introduced into the flow path 103 in advance, so that the time until the centrifugal force is stabilized can be increased.

The method for introducing the solution different from the droplet raw material (the aqueous solution stored in the container 102) into the flow path 103 is as follows. In the case of oil, for example, the droplet outlet of the droplet recovery container 109 is closed and the solution inlet of the container 102 is opened. Then, by extruding the oil from the container 104, the oil can be introduced into the flow path 103 from the flow paths 105 and 106 via the flow path connection portion 107. In the case of a solution dyed with a pigment, for example, first, for example, a droplet outlet of the droplet recovery container 109 is opened. Then, the dye-containing aqueous solution can be introduced into the channel 103 by putting the dye-containing aqueous solution into the container 102 and pushing it out of the container 102 into the channel 103.

(Ii) Step 302
The operator rotates the droplet generation disk 101 and moves the aqueous solution (droplet raw material) contained in the container 102 to the flow path 103 by the centrifugal force generated thereby.

At this stage, the centrifugal force due to rotation is not yet stable, and the solution (liquid different from the raw material) previously introduced into the flow path 103 is discharged to the droplet collection container 109.

(Iii) Step 303
The operator continues the rotation of the droplet generation disk 101 and moves the aqueous solution of the droplet raw material through the flow path 103 to the flow path connection portion 107 by the centrifugal force of rotation to generate a droplet. When the droplet generation disk 101 is rotated, the oil stored in the container 104 in addition to the aqueous solution stored in the container 102 passes through the flow paths 105 and 106 and reaches the flow path connection portion 107. A predetermined amount of the solution discharged from the flow path connection portion 107 (solution of the droplet generation raw material) is mixed with oil in the flow path connection portion 107 and becomes spherical in the oil. In this way, droplets are generated.

(Iv) Step 304
After the droplet generation disk 101 continues to rotate for a predetermined time or after droplets are generated for all of the solution contained in the container 102, the operator recovers the droplets generated from the droplet recovery container 109. To do.

<System configuration example>
FIG. 4 is a diagram showing a configuration example of a system (liquid processing system) for generating droplets and measuring fluorescence through PCR.

The system includes, for example, a droplet generation device 120, a PCR device 121, a droplet measurement device 122, and a control device 123. The droplet generation disc 101 described in FIG. 1 is set in a droplet generation device 120 having a centrifugal mechanism, and droplet generation using centrifugal force is performed. The generated droplets accumulate in the oil in the droplet collection container 109. Droplets and oil in the droplet collection container 109 are transferred to, for example, a tube by an operator, for example, and set in a PCR apparatus 121 that performs a PCR method, which is one method of nucleic acid amplification. For example, when the operator operates the PCR device 121 in which a tube containing droplets is set, a nucleic acid amplification reaction is performed. The tube containing the droplet after nucleic acid amplification is transferred to the droplet measuring device 122 by an operator, for example, and set. Then, the droplets in the tube are discharged from the tube one by one by a pump (not shown). Each droplet is irradiated with laser light, and a signal for each droplet such as fluorescence is measured. Thereby, the density | concentration and arrangement | sequence information of the nucleic acid included in the inside of a droplet can be obtained. Operations of the droplet generation device 120, the PCR device 121, and the droplet measurement device 122 can be controlled by the control device 123. However, each of the droplet generation device 120, the PCR device 121, and the droplet measurement device 122 may be configured to include a control device. In the example of FIG. 2, the operator transfers the droplet to the next apparatus, but the system may be configured so that all these operations can be performed automatically.

<About droplet digital PCR>
A method of dividing a nucleic acid molecule in a solution into a large number of droplets, performing PCR, and counting the presence or absence of the signal is called droplet digital PCR, and is generated by the droplet generator 120 according to this embodiment. One of the fields of application of the prepared droplets.

In the droplet digital PCR, it is necessary to divide the droplet so that the number of nucleic acid molecules to be measured is one molecule in droplets having a diameter of several micrometers to several hundred micrometers. On the other hand, in the droplet generation device according to the present embodiment, when the aqueous solution that is the raw material of the droplet is pushed out from the flow channel 103 to the flow channel connecting portion 107 by centrifugal force, the size of the flow channel 103, particularly the size of the outlet, Droplets of the same degree or before and after are generated. Therefore, in order to generate droplets so that the number of nucleic acid molecules becomes one molecule, it is desirable that the size (diameter or width) of the channel 103, particularly the size of the outlet, be 1 micrometer to 1 millimeter. More preferably, the size of the flow path 103, particularly the size of the outlet, is 100 micrometers or less, and more preferably 30 micrometers or less. In droplet digital PCR, increasing the number of droplets that can be created from a given solution enables accurate counting of low-concentration target molecules (for example, DNA sequences with a small number in the solution). is there. In addition, since the flow path production accuracy is usually on the order of microns, in order to suppress variations in the size of the droplets, it is desirable that the droplet size is effectively about 5 micrometers or more. Summarizing the case of application to droplet digital PCR, the outlet size (diameter or width) of the channel 103 is allowed to be 1 micrometer or more and 1 millimeter, preferably 1 micrometer or more and 100 micrometers or less, and more preferably. Is 5 micrometers or more and 30 micrometers or less.

(2) Second Embodiment FIG. 5 is a diagram showing a basic configuration of a main part of a droplet generating apparatus according to a second embodiment of the present invention. FIG. 5 also shows the minimum required configuration of one unit (basic unit device) formed on the droplet generation disk 201 of the droplet generation device, as in FIG. Actually, one or more such basic unit devices are arranged on the droplet generating disk 201 having the rotation center 110. The difference from the first embodiment is that there are a plurality of droplet generation locations (N: only two are shown in FIG. 5, but there may be three or more), and the solution channels (flow in FIG. 5). There is a region 240 where the channel 203 and the channel 223) effectively overlap. Note that “effectively overlap” means that when a convex figure circumscribing the flow path is considered, the circumscribed figures of adjacent flow paths overlap each other. By providing the overlapping region 240, it is possible to effectively use a limited area on the rotating disk and install a larger number of droplet generation units, thereby increasing the number and types of droplets that can be generated simultaneously. be able to.

As shown in FIG. 5, the basic unit of the droplet generating device according to the second embodiment is composed of two containers 202 and 222 for storing an aqueous solution of a droplet generating raw material, and a container (aqueous solution container) 202. An extended flow path (solution flow path) 203, a flow path (solution flow path) 223 extended from a container (aqueous solution container) 222, and a container (oil) for storing liquid (oil) outside the droplets Container) 204, flow paths (oil flow paths) 205 and 225 extending from the container 104, and two liquid droplet collection containers 209 and 229 for collecting the generated liquid droplets Yes.

The containers 202, 222, and 204 are arranged closer to the center 210 of the droplet generation disk 201 than the droplet collection containers 209 and 229. That is, the containers 202, 222, and 204 are disposed on the inner periphery side of the droplet generation disk 201, and the droplet collection containers 209 and 229 are disposed on the outer periphery side of the droplet generation disk 201.

The container 202 is connected to the flow path 203 from the container outlet 211. The container 222 is connected to the flow path 223 from the container outlet 231. The container 204 is connected to the flow paths 205 and 225 from the container outlets 212 and 213, respectively. The flow path 205 is connected to the flow path 203 by a flow path connection portion 207. The flow path 225 is connected to the flow path 223 by the flow path connection portion 227. The channels 203 and 205 are connected to the droplet recovery container 209 from the channel connection unit 207 via the channel (droplet channel) 208. The channels 223 and 225 are connected to the droplet collection container 229 from the channel connection unit 227 via the channel (droplet channel) 228.

In the basic unit of the droplet generating apparatus having each component as described above, the lengths of the flow paths (solution flow paths) 203 and 223 are connected to the container outlet 211 and the flow path as in the first embodiment. It is longer than the linear distance between the part 207 and the linear distance between the container outlet 231 and the flow path connecting part 227. Various forms other than the one shown in FIG. 5 are conceivable as to how the flow paths 203 and 223 meander. As in the first embodiment, as long as a part of the flow paths 203 and 223 is not located on the inner peripheral side of the droplet generation disk 201 with respect to the container outlets 211 and 231, the flow paths 203 and 231 are restricted to meandering. There is no. Further, the meandering shapes of the channel 203 and the channel 223 may be different as long as the overlapping region 240 is formed.

When N containers for storing the raw material aqueous solution, droplet recovery containers, and N solution channels are provided, for example, N oil channels and N solutions extending from one oil container are used. The flow paths are respectively connected by N flow path connection portions. Further, N droplet channels are respectively extended from the channel connection part, and the N droplet channels are connected to the N droplet recovery containers, respectively. Also in this case, as shown by a region 240 in FIG. 5, each adjacent solution flow path is configured to meander while forming an overlapping region. In this case, the number of overlapping areas is N−1 when the overlapping areas in FIG. 5 are counted as one. Regarding the oil container, one droplet generating disk 201 having a large capacity may be provided, or one common one is provided in units of k (k <N) droplet collecting containers. You may do it.

(3) Summary In this embodiment, the length of the flow path (the first flow paths 103, 203, and 223) through which the first liquid (the aqueous solution containing the raw material of the droplets) passes is the liquid storage section ( Flow path connection points between the first flow path and the second flow path (flow paths 105, 106, 205, 225 through which oil passes) from the outlets (111, 211, 231) of the containers 102, 202, 222) This is longer than the linear distance to the point where a droplet is generated. Preferably, the length of the first channel is at least twice the linear distance. By doing in this way, the time for the liquid droplet raw material to reach the liquid droplet generation location can be set longer than the time until the centrifugal force generated by rotating the liquid droplet generation disk is stabilized, Variations in the size of the generated droplets can be suppressed.

The shape of the first flow path may be, for example, a meandering shape or a three-dimensional shape such as a spiral shape. Although any shape can be adopted for the first flow path, it is desirable that an arbitrary position of the first flow path is on the outer peripheral side of the outlet of the solution storage unit. As described above, since the first flow path has a high degree of freedom, it is possible to reliably align the sizes of the droplets while meeting the needs of the user regarding the configuration of the droplet generation device.

However, it is necessary that the direction vector from the outlet of the liquid container to the flow path connection portion has a component with respect to the direction in which the centrifugal force acts. By having the component, droplets having a uniform size can be reliably generated.

The size of the generated droplet can be adjusted by the width (diameter) of the flow path. In order to generate a droplet suitable for droplet digital PCR, the width of the first channel at the channel connection point is, for example, not less than 1 micrometer and not more than 1 millimeter, preferably not less than 5 micrometers and not more than 1 millimeter, Preferably they are 5 micrometers or more and 30 micrometers or less. By doing so, it is possible to generate droplets having an effective size for the droplet digital PCR process.

One or both of the first flow path and the second flow path are arranged on the droplet generation disk (101). Alternatively, a plurality of sets of the first flow path and the second flow path may be provided and disposed on the droplet generation disk. In this case, at least adjacent first channels among the plurality of first channels are arranged on the droplet generation disk so as to have an overlapping region. By doing in this way, more first flow paths can be arranged in the droplet generation flow path, and more uniform size droplets can be generated efficiently.

Note that the present invention is not limited to the above-described embodiment, and includes various modifications. For example, the above-described embodiments have been described in detail for easy understanding of the present invention, and are not necessarily limited to those having all the configurations described. Further, a part of the configuration of an embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of an embodiment. In addition, it is possible to add, delete, and replace other configurations for a part of the configuration of each embodiment.

101, 201 Droplet generation discs 102, 202, 222 Containers 103, 203, 223 Flow path (first flow path)
104, 204 Container 105, 106 Channel (second channel)
107, 207, 227 Channel connection part 108, 208, 228 Channel 109, 209, 229 Droplet collection container 110, 210 Rotation center 111, 211, 231 Outlet of containers 102, 202, 222 Droplet generation device 121 PCR Device 122 Droplet measuring device 123 Control device

Claims (15)

A droplet generator that generates droplets using centrifugal force generated by rotating a disk,
A liquid storage section for storing the first liquid;
A first flow path that is connected to an outlet of the liquid container and through which the first liquid flows;
A second flow path through which a second liquid different from the first liquid flows,
The first channel and the second channel are connected at a channel connection location,
The length of the said 1st flow path is a droplet production | generation apparatus longer than the linear distance from the exit of the said liquid accommodating part to the said flow path connection location. In claim 1,
A droplet generating device that generates droplets of the first liquid at the flow path connection portion. In claim 1,
The length of the said 1st flow path is a droplet production | generation apparatus which is 2 times or more of the said linear distance. In claim 1,
The first flow path is a droplet generation device that meanders from the outlet of the liquid storage section to the flow path connection portion. In claim 1,
At least one of the first flow path and the second flow path is a droplet generating device arranged on the disk. In claim 1,
The first flow path is a droplet generation device arranged three-dimensionally. In claim 1,
A droplet generating apparatus, wherein a direction vector from an outlet of the liquid storage unit to the flow path connection portion has a component with respect to a direction in which the centrifugal force acts. In claim 1,
The droplet generating device, wherein the width of the first channel is 1 micrometer or more and 1 millimeter or less. In claim 1,
The droplet generating device, wherein a width of the first flow path at the flow path connecting portion is not less than 5 micrometers and not more than 1 millimeter. In claim 1,
The droplet generating device, wherein a width of the first flow path at the flow path connecting portion is not less than 5 micrometers and not more than 30 micrometers. In claim 5,
Having a plurality of sets of the first flow path and the second flow path,
The droplet generation device, wherein at least adjacent first channels among the plurality of first channels included in the plurality of sets are arranged on the disk while having an overlapping region. A method of generating droplets using the droplet generator of claim 1, comprising:
Introducing a third liquid different from the first liquid into the first flow path;
Moving the liquid different from the first liquid to the flow path connection location by centrifugal force generated by rotating the disk;
Continuing the movement of the third liquid to the flow path connection location until the centrifugal force is at least stable;
A step of moving the first liquid from the liquid container to the first flow path by the centrifugal force;
A step of generating droplets by mixing the first liquid and the second liquid at the flow path connection portion in a state where the centrifugal force is stable;
Including a method. In claim 12,
The method, wherein the third liquid is the same liquid as the second liquid, or an aqueous solution containing a pigment or a fluorescent substance different from the color of the first liquid. A liquid processing system for processing a predetermined aqueous solution,
A droplet generator for generating droplets of the predetermined aqueous solution;
A nucleic acid amplification device that performs nucleic acid amplification using a PCR reaction on the droplet generated by the droplet generation device, and
The droplet generator is
A liquid storage section for storing the first liquid;
A first flow path that is connected to an outlet of the liquid container and through which the first liquid flows;
A second flow path through which a second liquid different from the first liquid flows,
The first channel and the second channel are connected at a channel connection location,
The length of the said 1st flow path is a liquid processing system longer than the linear distance from the exit of the said liquid accommodating part to the said flow path connection location. In claim 14,
Furthermore, the liquid processing system which has a droplet measuring device which measures the predetermined signal for every droplet amplified by the nucleic acid amplification device.

Images