Droplet generator

Abstract

The present disclosure discloses a droplet generating device that generates droplets using a prepared PCR reaction solution and oil. In particular, the droplet generating device may include: a pump providing negative pressure; a movable rigid body having a cubic shaped body and comprising a plurality of pressure applying ports and at least one pump connecting port; a flexible tube connecting the pump and the at least one pump connecting port; a motor providing mechanical force; and a mechanical mechanism that moves the movable rigid body along a first axis using the mechanical force provided from the motor.

Description

Technology Field

[0001] The present disclosure relates to a droplet generating device. More specifically, it relates to a droplet generating device capable of stably applying pressure to a droplet generating cartridge in which PCR reaction solution and oil are dispensed to generate droplets. Background Technology

[0002] Polymerase Chain Reaction (PCR) is a molecular biological technique that replicates and amplifies desired portions of collected DNA. PCR allows researchers to selectively amplify specific DNA fragments from solutions containing extremely complex and trace amounts of DNA, such as the human genome. Additionally, it offers the advantages of a short amplification time, a simple experimental procedure, and the ability to perform amplification using fully automated machines. Consequently, PCR is widely used across various fields involving DNA processing, including molecular biology, medicine, forensic science, and biological classification.

[0003] Meanwhile, PCR can be classified into first-generation PCR, which qualitatively analyzes genes such as collected DNA through electrophoresis; second-generation real-time PCR, which can perform both qualitative and quantitative analysis of genes; and digital PCR (dPCR), which generates genes into tens of thousands of droplets, detects the fluorescence of the droplets, and performs qualitative and quantitative analysis of genes.

[0004] Among these, digital PCR can analyze the status of the collected genes, the onset of disease, or infection by detecting fluorescence from each of the amplified droplets and counting the number of positive and negative droplets.

[0005] Meanwhile, it is important to accurately count the number of positive and negative droplets in digital PCR. However, if the size of the generated droplets is not uniform, the number of samples or fluorescent substances contained in each droplet may differ. If the number of fluorescent substances or samples varies, the intensity of the fluorescence emitted when each droplet is positive may differ. This, in turn, can be a factor that reduces the reliability of distinguishing between positive and negative droplets.

[0006] Therefore, in order to accurately determine the number of positive and negative droplets, it is important that the size of the droplets produced during generation is as consistent as possible. The problem to be solved

[0007] The present disclosure relates to a droplet generating device.

[0008] The problem that the present disclosure aims to solve is to provide a droplet generating device capable of providing stable pressure to a droplet generating cartridge so that the size of the droplets generated by mixing the PCR reaction solution and oil is constant.

[0009] The problems that the present disclosure aims to solve are not limited to those described above, and problems not mentioned will be clearly understood by those skilled in the art corresponding to the present disclosure from the present specification and the attached drawings. means of solving the problem

[0010] A droplet generating device for generating droplets using a prepared PCR reaction solution and oil according to the present disclosure may include: a pump providing negative pressure; a movable rigid body having a cubic shaped body and comprising a plurality of pressure applying ports and at least one pump connecting port, wherein the plurality of pressure applying ports and the at least one pump connecting port are formed on the surface of the movable rigid body, and the movable rigid body further comprises an airway network formed inside the movable rigid body to connect the plurality of pressure applying ports and the at least one pump connecting port; a flexible tube connecting the pump and the at least one pump connecting port; a motor providing mechanical force; and a mechanical mechanism for moving the movable rigid body along a first axis using the mechanical force provided from the motor.

[0011] At this time, the flexibility of the flexible tube allows the fluid connection between the pump and the at least one pump connection port to be maintained regardless of the position of the movable rigid body, and the rigidity of the air passage mesh allows the negative pressure provided by the pump to be stably applied to a plurality of droplet generation reservoirs included in the droplet generation cartridge. Effects of the invention

[0012] According to one embodiment of the present disclosure, a droplet generating device can generate droplets of uniform size.

[0013] The effects according to the present disclosure are not limited to the effects described above, and unmentioned effects will be clearly understood by those skilled in the art from the present disclosure and the attached drawings. Brief explanation of the drawing

[0014] FIG. 1 shows a droplet generator cartridge used in an embodiment of the present disclosure. Figure 2 is intended to explain the problems of a conventional droplet generating device. FIGS. 3 to 5 are drawings for explaining a droplet generating device according to a first embodiment of the present disclosure. FIGS. 6 and 7 are drawings for explaining a droplet generating device according to a second embodiment of the present disclosure. FIGS. 8 and 9 are drawings for explaining a droplet generating device according to a third embodiment of the present disclosure. FIGS. 10 to 13 are drawings for explaining the components included in a droplet generating device according to an embodiment of the present disclosure. FIGS. 14 and 15 are for explaining the operation of a droplet generating device according to an embodiment of the present disclosure. FIGS. 16 and 17 show an experimental design for comparing the droplet generation results of the embodiments of the present disclosure and a conventional droplet generation device. FIGS. 18 to 30 show experimental results of generating droplets using embodiments of the present disclosure and a conventional droplet generating device. Specific details for implementing the invention

[0015] The aforementioned objects, features, and advantages of the present disclosure will become more apparent from the following detailed description in conjunction with the accompanying drawings. However, as the present disclosure is subject to various modifications and may have various embodiments, specific embodiments are illustrated in the drawings and described in detail below.

[0016] The embodiments described in this specification are intended to clearly explain the concept of this disclosure to those skilled in the art to which this disclosure belongs; therefore, this disclosure is not limited by the embodiments described in this specification, and the scope of this disclosure should be interpreted to include modifications or variations that do not depart from the concept of this disclosure.

[0017] The drawings attached to this specification are intended to facilitate the explanation of the present disclosure, and the shapes depicted in the drawings may be exaggerated as necessary to aid in understanding the present disclosure; therefore, the present disclosure is not limited by the drawings.

[0018] If it is determined that a detailed description of known functions or configurations related to the present disclosure could unnecessarily obscure the essence of the present disclosure, such detailed description is omitted. Furthermore, numbers used in the description of this specification (e.g., First, Second, etc.) are merely identifiers to distinguish one component from another.

[0019] Furthermore, the suffixes "unit," "module," and "part" used for components in the following description are assigned or used interchangeably solely for the ease of drafting the specification, and do not inherently possess distinct meanings or roles.

[0021] A droplet generating device for generating droplets using a prepared PCR reaction solution and oil according to the present disclosure may include: a pump providing negative pressure; a movable rigid body having a cubic shaped body and comprising a plurality of pressure applying ports and at least one pump connecting port, a flexible tube connecting the pump and the at least one pump connecting port; a motor providing mechanical force; and a mechanical mechanism for moving the movable rigid body along a first axis using the mechanical force provided from the motor.

[0022] Here, the plurality of pressure application ports and the at least one pump connection port are formed on the surface of the movable rigid body, and the movable rigid body is formed inside the movable rigid body and may further include an airway network connecting the plurality of pressure application ports and the at least one pump connection port.

[0023] In addition, the flexibility of the flexible tube allows the fluid connection between the pump and the at least one pump connection port to be maintained regardless of the position of the movable rigid body, and the rigidity of the air passage mesh allows the negative pressure generated by the pump to be stably applied to a plurality of droplet generation reservoirs included in the droplet generation cartridge.

[0024] Meanwhile, the droplet generating cartridge comprises a plurality of PCR reaction solution reservoirs into which PCR reaction solution is dispensed, a plurality of oil reservoirs into which oil is dispensed, and the plurality of droplet generating reservoirs, wherein the negative pressure stably applied to the plurality of droplet generating reservoirs allows the PCR reaction solutions discharged from the plurality of PCR reaction solution reservoirs and the oils discharged from the plurality of oil reservoirs to meet and form droplets, and the size of the droplets stored in the plurality of droplet generating reservoirs can be made constant.

[0025] In addition, the plurality of pressure application ports may be located on the lower surface of the movable rigid body to apply negative pressure to the plurality of droplet generation reservoirs.

[0026] In addition, the first axis may be perpendicular to the surface where the plurality of pressure application ports are formed.

[0027] Additionally, the movable rigid body further includes a valve that allows negative pressure provided from the pump to be applied to the plurality of droplet generating reservoirs; and the air passage network may include an air conduit network connecting the valve and the plurality of pressure application ports and an air conduit connecting the valve and the at least one pump connection port.

[0028] Additionally, the droplet generating device may further include a controller that controls the operation of the pump and the valve; the controller may control the pump so that the provision of the negative pressure begins at a first time point, and may open the valve so that the negative pressure provided from the pump is applied to the plurality of droplet generating reservoirs after a first time interval from the first time point. At this time, the first time interval may be a preset.

[0029] Additionally, the droplet generating device may further include a position sensor for sensing the position of the movable rigid body; and a controller for controlling the motor, wherein the controller may control the motor based on the sensing of the position sensor so that the plurality of pressure application ports can be fluidly connected to the plurality of droplet generating reservoirs, thereby causing the mechanical mechanism to move the movable rigid body downward along the first axis.

[0030] In addition, the controller can control the motor based on the sensing of the position sensor so that the plurality of pressure application ports cannot be fluidly connected to the plurality of droplet generation reservoirs, thereby causing the mechanical mechanism to move the movable rigid body upward along the first axis.

[0032] [General Digital PCR]

[0033] Digital PCR exhibits a sensitivity approximately 1,000 times higher than real-time PCR and is suitable for analyzing target genes even in complex mixtures. The high sensitivity of digital PCR allows it to be more effective than the real-time PCR method in cases where the concentration of the target in the sample is very low.

[0034] In addition, digital PCR is highly advantageous for the quantification of target DNA compared to real-time PCR.

[0035] To perform digital PCR, processes are fundamentally required to divide an analyte sample (solution) containing DNA into predetermined volumes and to allow an amplification reaction of the target DNA to occur within the divided sample (solution). In particular, digital PCR methods can be classified in various ways depending on the method of dividing the sample into predetermined volumes. The present disclosure relates to droplet digital PCR, which uses a method of dividing the sample into droplets.

[0037] To perform droplet digital PCR, the following three processes are largely followed.

[0039] (1) Droplet generation step

[0040] (a) a sample containing target DNA to be amplified and (b) a PCR reaction solution comprising i) primers for amplifying the target DNA, ii) a fluorescent probe or fluorescent dye, iii) dNTP (deoxynucleoside triphosphate) used as a material for the amplicon, iv) polymerase, etc. are prepared. For example, fluorescent probes or fluorescent dyes may include FAM, HEX, VIC, TAMRA, EvaGreen, etc. Additionally, the sample refers to the result of pretreatment necessary for PCR analysis of blood, tissue, cells, saliva, etc. collected from a subject. In particular, the sample contains DNA to be analyzed.

[0042] FIG. 1 shows a droplet generating cartridge (100) for generating droplets using a PCR reaction solution and oil. FIG. 1(a) shows a top view of the droplet generating cartridge (100), and FIG. 1(b) shows a bottom view of the droplet generating cartridge (100).

[0043] Referring to FIG. 1(a), the droplet generating cartridge (100) may include at least one droplet generating unit (110). The droplet generating unit (110) included in the droplet generating cartridge (100) may be a plurality of.

[0044] The droplet generating unit (110) includes an oil reservoir (111), a PCR reaction solution reservoir (112), and a droplet reservoir (113). Oil is dispensed into at least one oil reservoir (111) included in the droplet generating cartridge, and PCR reaction solution is dispensed into at least one PCR reaction solution reservoir (112) included in the droplet generating cartridge.

[0045] Meanwhile, when negative pressure is applied to the droplet storage (113), the oil stored in the oil storage (111) and the PCR reaction solution stored in the PCR reaction solution storage (112) move to the droplet storage (113), thereby generating droplets.

[0046] Alternatively, when positive pressure is applied to the oil storage (111) and the PCR reaction solution storage (112), the oil stored in the oil storage (111) and the PCR reaction solution stored in the PCR reaction solution storage (112) move to the droplet storage (113) and droplets are generated.

[0047] FIG. 1(b) is a lower view of a droplet generating cartridge (100) to explain in detail the process of generating droplets in a droplet generating unit (110).

[0048] Referring to FIG. 1(b), the droplet generation unit (110) further includes a droplet generation junction (130), a plurality of oil transfer channels (121) extending between an oil reservoir (111) and the droplet generation junction (130), a PCR reaction solution transfer channel (122) extending between a PCR reaction solution reservoir (112) and the droplet generation junction (130), and a droplet transfer channel (123) extending between a droplet reservoir (113) and the droplet generation junction (130). That is, the plurality of oil transfer channels (121), the PCR reaction solution transfer channel (122), and the droplet transfer channel (123) join at the droplet generation junction (130).

[0049] When negative pressure is applied to the droplet storage (113) or positive pressure is applied to the oil storage (111) and the PCR reaction solution storage (122), the oil stored in the oil storage (111) moves to the droplet generation junction (130) through a plurality of oil transfer channels (121), and the PCR reaction solution stored in the PCR reaction solution storage (122) moves to the droplet generation junction (130) through the PCR reaction solution transfer channel (122). The PCR reaction solution and oil that meet at the droplet generation junction (130) are combined so that the oil surrounds the PCR reaction solution to generate a droplet. The generated droplet is then transferred to the droplet storage (113).

[0050] That is, the force that transports the PCR reaction solution and oil to meet at the liquid crystal generation junction (130) and transports them to the droplet storage (113) is generated by the negative pressure applied to the droplet storage (113) or the positive pressure applied to the oil storage (111) and the PCR reaction solution storage (122), and no other force acts.

[0051] Meanwhile, the method of generating droplets using PCR reaction solution and oil is based on microfluidics technology, but is not limited to this.

[0053] (2) Droplet amplification step

[0054] As described above, after the droplets are generated, repetitive heat treatment is performed on the generated droplets according to a predetermined thermal cycle. Accordingly, the target DNA can be amplified within the PCR reaction solution contained in each droplet. Of course, DNA amplification occurs within droplets containing the target DNA, but not within droplets that do not contain the target DNA. Basically, the aforementioned positive droplets refer to droplets containing the target DNA, and negative droplets refer to droplets that do not contain the target DNA.

[0056] (3) Droplet detection step

[0057] Meanwhile, generally, when attempting to detect two or more target DNAs using two or more fluorescent materials, PCR reagents can be designed so that each of the different fluorescences corresponds to a different target DNA. That is, when the first target DNA is amplified, the fluorescence emitted from the amplified amplicon is formed in a first wavelength band, and when the second target DNA is amplified, the fluorescence emitted from the amplified amplicon is formed in a second wavelength band distinct from the first wavelength band. Thus, a PCR device having multiple fluorescence detectors can detect multiple target DNAs from a single sample.

[0058] In the case of digital PCR, since the PCR reaction takes place within a single droplet, detecting the type (wavelength) of fluorescence emitted from the droplet after the amplification reaction is complete provides information about the target DNA contained within that droplet. Therefore, for digital PCR equipment, it is important to accurately detect the type of fluorescence emitted from each specific droplet.

[0059] Fluorescence is detected from droplets (positive droplets) containing amplified target DNA using a fluorescence detector. That is, the fluorescence detector emits light (e.g., a laser or LED) toward the droplets, and can detect the wavelength of the fluorescence radiated as the emitted light interacts with the fluorescent material possessed by the droplets.

[0060] In this case, a device including a fluorescence detector can count droplets by fluorescent material according to the wavelength of fluorescence corresponding to the fluorescent material. For example, the device can individually count the number of droplets having FAM, the number of droplets having HEX, the number of droplets having VIC, the number of droplets having TAMRA, and the number of droplets having EvaGreen among the amplified droplets according to the wavelength detected by the fluorescence detector. For example, the detector of the fluorescence detector can detect only specific wavelengths. In other words, the detector may include a filter that passes only specific wavelengths, and accordingly, can detect only the wavelength emitted by a specific fluorescent material.

[0061] Accordingly, each of the multiple fluorescence detectors can detect distinct wavelengths, and the device can individually count the number of droplets having a fluorescent material corresponding to the wavelength detectable by each detector among the amplified droplets, based on the number of times each detector detects the wavelength corresponding to it.

[0062] As a specific example, if the intensity of fluorescence detected by the fluorescence detector exceeds a certain threshold, the counting number of droplets of fluorescent material corresponding to the wavelength detectable by the fluorescence detector can be increased.

[0063] The device can analyze the biological characteristics of a sample based on the number of droplets counted by fluorescent material.

[0065] Meanwhile, the aforementioned droplet generation step, droplet amplification step, and droplet detection step may each be performed separately in different devices. For example, the droplet generation step may be performed by a first device, the droplet amplification step by a second device, and the droplet detection step by a third device.

[0066] As another example, the aforementioned droplet generation step, droplet amplification step, and droplet detection step may be performed integrally in a single specific device.

[0067] As another example, two of the above-described droplet generation step, droplet amplification step, and droplet detection step may be performed in one device, and the remaining one may be performed in another device. For example, the droplet generation step and the droplet amplification step may be performed in a fourth device, and the droplet detection step may be performed in the third device. As another example, the droplet generation step may be performed in the first device, and the droplet amplification step and the droplet detection step may be performed in a fifth device.

[0069] Meanwhile, the droplet generating device described in this disclosure is a device that performs a droplet generating step. However, such a droplet generating device is not required to perform only the droplet generating step. That is, the droplet generating device may be the first device described above, a specific device, or a fourth device. Therefore, the droplet generating device is sufficient if it includes the configurations described in the present disclosure below and is capable of performing functions and operations. In other words, the droplet generating device of this disclosure may include at least one other configuration other than the configurations described in this disclosure, and may also perform other functions and operations other than those described in this disclosure.

[0071] [Droplet generator]

[0072] As described above, in order for a droplet to be generated in the droplet generating cartridge (100), pressure must be provided to the droplet generating cartridge (100) so that the PCR reaction solution stored in the PCR reaction solution reservoir (122) and the oil stored in the oil reservoir (111) can move to the droplet reservoir (113).

[0073] The droplet generating device described in the present disclosure is a device that functions to generate droplets in the droplet generating cartridge (100) by applying the pressure to the droplet generating cartridge.

[0074] For example, the droplet generating device is a device that applies pressure generated by a pump to a droplet generating cartridge (100) through a plurality of pressure application ports so that droplets can be generated in the droplet storage (113) of the droplet generating cartridge (100).

[0075] As described above, the pressure applied to the droplet generating cartridge (100) may be negative pressure applied to the droplet storage (113) or positive pressure applied to the oil storage (111) and the PCR reaction solution storage (122); however, the following description assumes that the droplet generating cartridge (100) applies negative pressure to the droplet storage (113). However, the following description does not mean that an embodiment in which the droplet generating device applies positive pressure to the oil storage (111) and the PCR reaction solution storage (122) is excluded; rather, it is clear that the subject matter described by the present disclosure can also be applied to an embodiment in which the droplet generating device applies positive pressure to the oil storage (111) and the PCR reaction solution storage (122).

[0077] [Problems with conventional droplet generating devices]

[0078] Figure 2 shows a method for generating droplets in a conventional droplet generating device.

[0079] Referring to FIG. 2, the droplet generating device includes a pump (200) and a pressure applying structure. Here, the pressure applying structure includes a plurality of pressure applying ports (310) and a flexible tube. Additionally, although not shown in FIG. 2, the droplet generating device may further include a motor. The droplet generating device can move the plurality of pressure applying ports (310) and / or the droplet generating cartridge (100) by controlling one or more motors connected to the pressure applying structure.

[0080] In the following description, the meaning that a plurality of pressure application ports (310) and / or droplet generating cartridges (100) move may mean that a droplet generating device controls one or more motors to move a plurality of pressure application ports (310) and / or droplet generating cartridges (100). Additionally, the meaning that a pump (200) generates pressure may mean that a droplet generating device controls a pump (200) to generate pressure.

[0081] The flexible tube transmits the pressure generated by the pump (200) to a plurality of pressure application ports (310). Additionally, the plurality of pressure application ports (310) apply the transmitted pressure to the droplet generating cartridge (100). For example, the plurality of pressure application ports (310) may apply negative pressure to the droplet reservoir (113) or apply positive pressure to the oil reservoir (111) and the PCR reaction solution reservoir (1120).

[0082] Referring to FIG. 2 (a), the droplet generating cartridge (100) moves into the droplet generating device. For example, the droplet generating cartridge (100) moves into the droplet generating device according to direction (1).

[0083] Additionally, the plurality of pressure application ports (310) move to a first position on the upper part of the droplet generating cartridge (100). At this time, the flexible tube moves according to the movement of the plurality of pressure application ports (310). For example, the flexible tube may deform (e.g., the flexible tube gradually straightens) until the plurality of pressure application ports (310) move according to the direction (2) and are positioned at the first position on the upper part of the droplet generating cartridge (100).

[0084] Referring to FIG. 2 (b), the plurality of pressure application ports (310) are moved downward to a second position and fluidly connected to the droplet generating cartridge (100). At this time, the flexible tube moves in accordance with the movement of the plurality of pressure application ports (310). For example, the flexible tube may move until the plurality of pressure application ports (310) are moved to a second position where they are fluidly connected to the droplet generating cartridge (100) according to the direction (3).

[0085] As described above, the plurality of pressure application ports (310) can be moved to a second position to be fluidly connected to the droplet generating cartridge (100). Additionally, when droplet generation is complete, the plurality of pressure application ports (310) can be moved in the opposite direction of direction (3) to a third position and then in the opposite direction of direction (2) to a fourth position to release the fluid connection with the droplet generating cartridge (100).

[0086] When the multiple pressure application ports (310) are moved to a position where they are fluidly connected to the droplet generating cartridge (100) or fluidly connected to the droplet generating cartridge (100), the flexible tube helps the multiple pressure application ports (310) move smoothly.

[0087] In other words, implementing the pressure transmission pathway network as a flexible tube is for the smooth movement of multiple pressure application ports (310).

[0089] Meanwhile, when a conventional droplet generating device generates droplets according to the process described above, a phenomenon occurs in which the droplet size is not generated uniformly. In particular, when vibration occurs in the droplet generating device due to a force provided from the outside of the droplet generating device, or when vibration occurs inside the droplet generating device due to components included in the droplet generating device (e.g., motor, pump), a phenomenon occurs in which the droplet size is not generated uniformly, and it is found that the greater the vibration generated, the greater the difference in size between the droplets.

[0090] The fact that the sizes of the droplets are not uniform may mean that the pressure applied to the droplet generating cartridge (100) is not stable.

[0091] Here, the pressure being stable means that the pressure is maintained at a constant level during the time interval in which pressure is applied to the droplet generating cartridge (100).

[0092] Here, maintaining constant pressure means that during the time interval in which pressure is applied to the droplet generating cartridge (100), the change in pressure changes within a first constant range and / or the amount of change in pressure per unit time changes within a second constant range.

[0093] On the other hand, the pressure being unstable (i.e., the pressure not being maintained at a constant level) means that the pressure applied to the droplet generating cartridge (100) changes beyond a first constant range during the time interval and / or the amount of change in pressure per unit time changes beyond a second constant range.

[0094] If droplets are not uniformly controlled during generation, the number of samples or fluorescent substances contained in each droplet may vary. Furthermore, if the number of fluorescent substances or samples in each droplet differs, the intensity of the fluorescence emitted may vary when each droplet is positive. This leads to a problem where the analysis results of digital PCR cannot be trusted.

[0095] Accordingly, a structure of a droplet generating device capable of controlling the size of the droplets to be uniform is required. In other words, a structure of a droplet generating device capable of controlling the pressure applied to the liquid crystal generating cartridge (100) to be stable is required.

[0097] In order to solve the aforementioned problem, the present disclosure proposes a method of implementing a pressure-transmitting pathway network (hereinafter referred to as the pressure-applying pathway network) between a plurality of pressure-applying ports and a pump such that at least a portion of the network has rigidity. In other words, the present disclosure proposes a method of implementing a pressure-transmitting pathway network implemented as a flexible tube in FIG. 2 such that at least a portion of the network has rigidity.

[0098] In addition, through this, we intend to provide a method in which the pressure generated when the pump (200) generates pressure is stably applied to the droplet generating cartridge (100).

[0100] Meanwhile, in the description above and the description below, the statement that the plurality of pressure application ports (310) and the droplet generating cartridge (100) are fluidly connected may mean that the plurality of pressure application ports (310) and the droplet storage (113) are fluidly connected. It has already been described above that the plurality of pressure application ports (310) and the droplet storage (113) are fluidly connected when the pump (200) generates negative pressure.

[0101] On the other hand, the fact that the plurality of pressure application ports (310) and the droplet generating cartridge (100) are fluidly connected may mean that the plurality of pressure application ports (310) are fluidly connected to the PCR reaction solution reservoir (122) and the oil reservoir (111). It has already been described above that the plurality of pressure application ports (310) and the PCR reaction solution reservoir (122) and the oil reservoir (111) are fluidly connected when the pump (200) generates positive pressure.

[0103] [Example 1: Implementation of the entire pressure-applying pathway network using rigid pipes]

[0104] Referring to FIGS. 3 through 5, the droplet generating device in Embodiment 1 includes a pump (200) and a pressure applying structure. Here, the pressure applying structure includes a plurality of pressure applying ports (310) and a pressure applying path network (320) fluidly connecting the plurality of pressure applying ports (310) and the pump (200). Additionally, although not shown in FIGS. 3 through 5, the droplet generating device may further include one or more motors. The droplet generating device may move the plurality of pressure applying ports (310) and / or the droplet generating cartridge (100) by controlling one or more motors connected to the pressure applying structure.

[0105] In the following description, the meaning that a plurality of pressure application ports (310) and / or droplet generating cartridges (100) move may mean that a droplet generating device controls one or more motors to move a plurality of pressure application ports (310) and / or droplet generating cartridges (100). Additionally, the meaning that a pump (200) generates pressure may mean that a droplet generating device controls a pump (200) to generate pressure.

[0107] In Embodiment 1, as shown in FIG. 3, a pressure application path network (320) fluidically connecting a plurality of pressure application ports (310) and a pump (200) is described as being implemented entirely with rigid pipes. At this time, the pressure application path network (320) may be implemented with one rigid pipe or with two or more rigid pipes. For example, a part of the pressure application path network (320) may be implemented with a first rigid pipe, and the remaining part may be implemented with a second rigid pipe.

[0108] In Embodiment 1, as shown in FIG. 4, the pressure application path network (320) is entirely implemented as rigid pipes, wherein a portion of the pressure application path network (320) is implemented as a length-fixed rigid pipe and the remaining portion is implemented as a length-variable rigid pipe. Additionally, in Embodiment 1, as shown in FIG. 5, the pressure application path network (320) is entirely implemented as a length-variable rigid pipe.

[0109] FIG. 4(a) shows one embodiment according to Example 1. Referring to FIG. 4(a), in Example 1, the pressure application path network (320) includes an air conduit network (321), an air conduit (322), and a valve (323).

[0110] The air pipe network (321) fluidically connects the plurality of pressure application ports (310) and the valve (323), and the air pipe (322) fluidly connects the valve (323) and the pump (200). The valve (323) is intended to open and close the pressure application path network (320). When the droplet generating device opens the valve (323), the pressure generated by the pump (200) is transmitted to the plurality of pressure application ports (310) through the pressure application path network (320). On the other hand, when the droplet generating device (323) closes the valve, the pressure generated by the pump (200) is not transmitted to the plurality of pressure application ports (310). That is, the valve (323) can allow the pressure generated from the pump (200) to be applied to the droplet generating cartridge (100) through the plurality of pressure application ports (310).

[0111] Meanwhile, in Example 1, the pressure generated by the pump (200) is transmitted to a plurality of pressure application ports (310), and the pressure generated by the pump (200) is applied to the droplet generating cartridge (100), which implies that the droplet generating device has opened the valve (323).

[0113] In the embodiment of Example 1 according to FIG. 4(a), the air pipe mesh (321) may be implemented as a fixed-length rigid pipe, and the air pipe (322) may be implemented as a variable-length rigid pipe. Additionally, the length of the first part (322a) of the air pipe (322) may be varied along the y-axis, and the length of the second part (322b) of the air pipe (322) may be varied along the x-axis.

[0114] Referring to FIG. 4(a), the droplet generating cartridge (100) can move into the droplet generating device according to direction (1). Additionally, a plurality of pressure application ports (310) can move to a first position above the droplet generating cartridge (100), and while the plurality of pressure application ports (310) move to the first position, the length of a second part (322b) of the air tube (322) can be extended according to direction (2).

[0115] Additionally, as the plurality of pressure application ports (310) move downward and move to a second position where the plurality of pressure application ports (310) are fluidly connected to the droplet generating cartridge (100), the length of the first part (322a) of the air tube (322) may be extended according to the direction (3).

[0116] As described above, a plurality of pressure application ports (310) can be moved to be fluidly connected to the droplet generating cartridge (100). Additionally, when droplet generation is completed, the plurality of pressure application ports (310) can be moved in the opposite direction of direction (3) to the first position and then moved in the opposite direction of direction (2) to the third position in order to release the fluid connection with the droplet generating cartridge (100).

[0117] While the plurality of pressure application ports (310) move in the opposite direction of direction (3) to the first position, the length of the first part (322a) of the air tube (322) gradually shortens. Also, while the plurality of pressure application ports (310) move in the opposite direction of direction (2) to the third position, the length of the second part (322b) of the air tube (322) gradually shortens.

[0119] As another example, only the length of the first part (322a) of the air pipe (322) implemented as a length-variable rigid pipe may be varied along the y-axis, and the length of the remaining part of the air pipe (322) excluding the first part (322a) may be fixed.

[0120] In this case, the plurality of pressure application ports (310) may not move along the x-axis but may only move along the y-axis. For example, in FIG. 4(a), as the droplet generating cartridge (100) moves into the droplet generating device according to the direction (1), the plurality of pressure application ports (310) located at the first position move downward, and while the plurality of pressure application ports (310) move to the second position where they are fluidly connected to the droplet generating cartridge (100), the length of the first part (322a) of the air tube (322) may be extended according to the direction (3).

[0121] Additionally, when droplet generation is complete, the multiple pressure application ports (310) can move in the opposite direction of the direction (3) to the first position to release the fluid connection with the droplet generation cartridge (100).

[0122] While the multiple pressure application ports (310) move in the opposite direction of the direction (3) to the first position, the length of the first part (322a) of the air tube (322) becomes shorter.

[0124] In the embodiment of Example 1 according to FIG. 4(b), the air pipe mesh (321) may be implemented as a length-variable rigid pipe, and the air pipe (322) may be implemented as a length-fixed rigid pipe. Additionally, the length of the first part (321a) of the air pipe mesh (321) may be varied along the y-axis, and the length of the second part (321b) of the air pipe mesh (321) may be varied along the x-axis.

[0125] Referring to FIG. 4(b), the droplet generating cartridge (100) can move into the droplet generating device according to direction (1). Additionally, a plurality of pressure application ports (310) can move to a first position above the droplet generating cartridge (100). While the plurality of pressure application ports (310) move to the first position, the length of the second part (321b) of the air pipe mesh (321) can be extended according to direction (2).

[0126] Additionally, while moving downward until a plurality of pressure application ports (310) are fluidly connected to a second position with the droplet generating cartridge (100), the length of the first part (321a) of the air pipe network (321) may be extended according to the direction (3).

[0127] As described above, a plurality of pressure application ports (310) can be moved to be fluidly connected to the droplet generating cartridge (100). Additionally, when droplet generation is completed, the plurality of pressure application ports (310) can be moved in the opposite direction of direction (3) to the first position and then moved in the opposite direction of direction (2) to the third position in order to release the fluid connection with the droplet generating cartridge (100). As the plurality of pressure application ports (310) move in the opposite direction of direction (3) to the first position, the length of the first part (321a) of the air pipe mesh (321) becomes progressively shorter. Additionally, as the plurality of pressure application ports (310) move in the opposite direction of direction (2) to the third position, the length of the second part (321b) of the air pipe mesh (321) becomes progressively shorter.

[0129] As another example, only the first part (321a) of the air pipe (321) implemented as a length-variable rigid pipe may have a variable length along the y-axis, and the rest of the air pipe (321) excluding the first part (321a) may have a fixed length.

[0130] In this case, the plurality of pressure application ports (310) may not move along the x-axis but may only move along the y-axis. For example, in FIG. 4(a), when the droplet generating cartridge (100) moves into the droplet generating device according to the direction (1), the plurality of pressure application ports (310) located at the first position move downward, and while the plurality of pressure application ports (310) move to the second position where they are fluidly connected to the droplet generating cartridge (100), the length of the first part (321a) of the air tube (321) may be extended according to the direction (3).

[0131] Additionally, when droplet generation is complete, the multiple pressure application ports (310) can move in the opposite direction of the direction (3) to the first position to release the fluid connection with the droplet generation cartridge (100).

[0132] While the multiple pressure application ports (310) move in the opposite direction of the direction (3) to the first position, the length of the first part (321a) of the air tube (321) becomes shorter.

[0134] In the implementation of Example 1 according to FIG. 5(a) and (b), both the air pipe mesh (321) and the air pipe (322) can be implemented as length-variable rigid pipes. In this case, in FIG. 5(a), the length of a part (321b) of the air pipe mesh (321) can be varied along the x-axis, and the length of a part (322a) of the air pipe (322) can be varied along the y-axis. In FIG. 5(b), the length of a part (321a) of the air pipe mesh (321) can be varied along the y-axis, and the length of a part (322b) of the air pipe (322) can be varied along the x-axis.

[0135] Referring to FIGS. 5(a) and (b), the droplet generating cartridge (100) can move into the droplet generating device according to the direction (1). Additionally, a plurality of pressure application ports (310) move to a first position above the droplet generating cartridge (100), and while the plurality of pressure application ports (310) move to the first position above the droplet generating cartridge (100), in FIG. 5(a), the length of a part (321b) of the air tube mesh (321) can be extended according to the direction (2), and in FIG. 5(b), the length of a part (322b) of the air tube (322) can be extended according to the direction (2).

[0136] Additionally, the plurality of pressure application ports (310) move downward until they are positioned at a second position fluidly connected to the droplet generating cartridge (100), and while the plurality of pressure application ports (310) are moving to the second position, in FIG. 5(a), the length of the second part (322a) of the air tube (322) is extended in the direction (3), and in FIG. 5(b), the length of the part (321a) of the air tube mesh (321) can be extended in the direction (3).

[0137] As described above, a plurality of pressure application ports (310) can be moved to be fluidly connected to the droplet generating cartridge (100). Additionally, when droplet generation is completed, the plurality of pressure application ports (310) can be moved in the opposite direction of direction (3) to the first position and then moved in the opposite direction of direction (2) to the third position in order to release the fluid connection with the droplet generating cartridge (100). As the plurality of pressure application ports (310) move in the opposite direction of direction (3) to the first position, the length of a part (322a) of the air tube (322) in FIG. 5(a) becomes progressively shorter, and the length of a part (321a) of the air tube mesh (321) in FIG. 5(b) becomes progressively shorter. Additionally, as the multiple pressure application ports (310) move in the opposite direction of the direction (2) to the third position, the length of a part (321b) of the air pipe mesh (321) in FIG. 5(a) becomes shorter, and the length of a part (322b) of the air pipe (322) in FIG. 5(b) becomes shorter.

[0139] Meanwhile, in Example 1, the length of the length-variable stiffness pipe can be varied in fixed length units according to the clock of a processor included in the droplet generating device and / or the unit angular velocity of one or more motors determined by the clock of said processor. That is, the length of the length-variable stiffness pipe may not be varied to be shorter than a fixed length unit.

[0140] Accordingly, in order to implement Example 1, the first distance between the first position and the third position and / or the second distance between the first position and the second position may be determined according to the predetermined length unit.

[0142] Meanwhile, in Example 1, the length of the variable-length stiffness pipe changes as the plurality of pressure application ports (310) move. This change in the length of the variable-length stiffness pipe ensures that the fluid connection between the pump (200) and the plurality of pressure application ports (310) is maintained by the change in the length of the variable-length stiffness pipe, regardless of the movement and position of the plurality of pressure application ports (310).

[0144] [Example 2: Designing part of the pressure application path network with rigid pipes]

[0145] Referring to FIGS. 6 and 7, in Embodiment 2, the droplet generating device includes a pump (200) and a pressure applying structure. Here, the pressure applying structure includes a plurality of pressure applying ports (310) and a pressure applying path network (320) fluidly connecting the plurality of pressure applying ports (310) and the pump (200). Additionally, although not shown in FIGS. 6 and 7, the droplet generating device may further include one or more motors. The droplet generating device can move the plurality of pressure applying ports (310) and / or the droplet generating cartridge (100) by controlling one or more motors connected to the pressure applying structure.

[0146] In the following description, the meaning that a plurality of pressure application ports (310) and / or droplet generating cartridges (100) move may mean that a droplet generating device controls one or more motors to move a plurality of pressure application ports (310) and / or droplet generating cartridges (100). Additionally, the meaning that a pump (200) provides pressure may mean that a droplet generating device controls a pump (200) to provide pressure.

[0148] In Example 2, as shown in FIG. 6, a portion of the pressure application path network (320) fluidly connecting a plurality of pressure application ports (310) and a pump (200) is implemented as a rigid pipe, and the remaining portion is implemented as a flexible tube.

[0149] FIG. 7 shows an implementation example according to Example 2. Referring to FIG. 7, in Example 2, the pressure application path network (320) includes an air conduit network (321), an air conduit (322), and a valve (323).

[0150] The air pipe network (321) fluidly connects the plurality of pressure application ports (310) and the valve (323), and the air pipe (322) fluidly connects the valve (323) and the pump (200). The description of the valve (323) is omitted as it is the same as the description of the valve in Example 1.

[0152] In the embodiment of Example 2 according to FIG. 7, the air pipe mesh (321) may be implemented as a rigid pipe, and the air pipe (322) may be implemented as a flexible tube.

[0153] Referring to FIG. 7, the droplet generating cartridge (100) can move into the droplet generating device according to direction (1). Additionally, a plurality of pressure application ports (310) move to a first position above the droplet generating cartridge (100). At this time, the air tube (322) (i.e., flexible tube) moves according to the movement of the plurality of pressure application ports (310). For example, the air tube (322) can be deformed (e.g., the flexible tube gradually straightened) until the plurality of pressure application ports (310) move according to direction (2) and are positioned at the first position above the droplet generating cartridge (100).

[0154] Additionally, the plurality of pressure application ports (310) move downward in the direction (3) until they are located at a second position where they are fluidly connected to the droplet generating cartridge (100), and the air tube (322) (i.e., flexible tube) moves in accordance with the movement of the plurality of pressure application ports (310). In other words, the air tube (322) (i.e., flexible tube) is deformed in accordance with the movement of the plurality of pressure application ports (310).

[0155] As described above, a plurality of pressure application ports (310) can be moved to be fluidly connected to a droplet generating cartridge (100). Additionally, when droplet generation is completed, the plurality of pressure application ports (310) can be moved in the opposite direction of direction (3) to the first position and then in the opposite direction of direction (2) to the third position in order to release the fluid connection with the droplet generating cartridge (100). While the plurality of pressure application ports (310) are moved in the opposite direction of direction (3) to the first position and in the opposite direction of direction (2) to the third position, the air tube (322) (i.e., flexible tube) moves and deforms according to the movement of the plurality of pressure application ports (310).

[0157] As another example, referring to FIG. 7, when a droplet generating cartridge (100) moves into a droplet generating device according to direction (1), a plurality of pressure application ports (310) located at the first position move downward according to direction (3) until they are located at a second position fluidly connected to the droplet generating cartridge (100), and an air tube (322) (i.e., a flexible tube) moves in accordance with the movement of the plurality of pressure application ports (310). In other words, the air tube (322) (i.e., a flexible tube) is deformed in accordance with the movement of the plurality of pressure application ports (310).

[0158] As described above, when droplet generation is complete, the plurality of pressure application ports (310) can move in the opposite direction (3) to the first position to release the fluid connection with the droplet generation cartridge (100). While the plurality of pressure application ports (310) are moving in the opposite direction (3) to the first position, the air tube (322) (i.e., flexible tube) moves and deforms according to the movement of the plurality of pressure application ports (310).

[0160] Meanwhile, in Example 2, as the plurality of pressure application ports (310) move, the flexible tube moves and deforms. This movement and deformation of the flexible tube ensures that the fluid connection between the pump (200) and the plurality of pressure application ports (310) is maintained regardless of the movement and position of the plurality of pressure application ports (310). Additionally, the flexibility of the flexible tube helps the plurality of pressure application ports (310) move smoothly.

[0162] [Example 3: Rigid Body]

[0163] Referring to FIGS. 8 and 9, in Example 3, the droplet generating device comprises a pump (200) and a pressure applying structure (320), wherein a portion of the pressure applying structure (320) is implemented as a rigid body (315) made using a rigid material.

[0164] Additionally, although not illustrated in FIGS. 8 and 9, the droplet generating device may further include one or more motors. The droplet generating device may move the rigid body (315) and / or the droplet generating cartridge (100) by controlling one or more motors connected to the pressure application structure.

[0165] In the following description, the meaning that the rigid body (315) and / or droplet generating cartridge (100) moves may mean that the droplet generating device controls one or more motors to move the rigid body (315) and / or droplet generating cartridge (100). Additionally, the meaning that the pump (200) generates pressure may mean that the droplet generating device controls the pump (200) to generate pressure.

[0167] Referring to FIGS. 8 (a) and (b), the rigid body (315) includes a plurality of pressure application ports (310), an airway network (325), and at least one pump connection port (322d) inside the rigid body (315). Referring to FIG. 8 (a), the airway network (325) includes an air pipe network (321), a valve (323), and a first air pipe (322c). The air pipe network (321) fluidly connects the plurality of pressure application ports (310) and the valve (323), and the first air pipe (322c) fluidly connects the valve and at least one pump connection port (324). The description of the valve (323) is omitted as it is the same as that described in Example 1.

[0168] Among the pressure application structure (300), the second air pipe (322d), which is the remaining part excluding the rigid body, is implemented as a flexible tube, and the second air pipe (322d) fluidly connects at least one pump connection port (324) and the pump (200).

[0169] Referring to FIG. 8(b), a plurality of pressure application ports (310) may be disposed on the lower surface of a rigid body (315) so as to be fluidly connected to a droplet generating cartridge (100).

[0171] FIG. 9 is intended to illustrate that a plurality of pressure application ports (310) disposed on the lower surface of a rigid body (315) are fluidly connected to a droplet generating cartridge (100).

[0172] Referring to FIG. 9, the droplet generating cartridge (100) can move into the droplet generating device according to direction (1). Additionally, the rigid body (315) moves to a first position on the upper part of the droplet generating cartridge (100) such that a plurality of pressure application ports (310) are on the same axis as the droplet reservoir (113) (or PCR reaction solution reservoir (112) and oil reservoir (111)) of the droplet generating cartridge (100). At this time, the second air tube (322d) (i.e., flexible tube) moves according to the movement of the rigid body (315). For example, the second air tube (322d) may deform (e.g., the flexible tube gradually straightens) until the rigid body (315) moves according to direction (2) and is positioned at the first position on the upper part of the droplet generating cartridge (100).

[0173] Additionally, the rigid body (315) moves downward in the direction (3) until it is positioned at a second location where it is fluidly connected to the droplet generating cartridge (100), and the second air tube (322d) (i.e., flexible tube) moves in accordance with the movement of the rigid body (315). In other words, the second air tube (322d) (i.e., flexible tube) deforms in accordance with the movement of the rigid body (315).

[0174] At this time, the fact that multiple pressure application ports (310) are on the same axis as the droplet storage (113) (or PCR reaction solution storage (112) and oil storage (111)) of the droplet generation cartridge (100) may mean that the center of a specific pressure application port and the center of a droplet storage that must be fluidly connected to said specific pressure application port are located on the same axis.

[0175] As described above, the rigid body (315) can move so that a plurality of pressure application ports (310) are fluidly connected to the droplet generating cartridge (100). Additionally, when droplet generation is complete, the rigid body (315) can move in the opposite direction of direction (3) to a first position and then move in the opposite direction of direction (2) to a third position to release the fluid connection with the droplet generating cartridge (100). While the rigid body (315) moves in the opposite direction of direction (3) to the first position and in the opposite direction of direction (2) to the third position, the air tube (322) (i.e., flexible tube) moves and deforms according to the movement of the rigid body (315).

[0177] As another example, referring to FIG. 8, when the droplet generating cartridge (100) moves into the droplet generating device according to direction (1), the rigid body (315) located at the first position moves downward according to direction (3) until it is located at a second position fluidly connected to the droplet generating cartridge (100), and the air tube (322) (i.e., flexible tube) moves in accordance with the movement of the rigid body (315). In other words, the air tube (322) (i.e., flexible tube) is deformed in accordance with the movement of the rigid body (315).

[0178] When droplet generation is complete, the rigid body (315) may move in the opposite direction (3) to the first position to release the fluid connection with the droplet generation cartridge (100). While the rigid body (315) moves in the opposite direction (3) to the first position, the air tube (322) (i.e., flexible tube) moves and deforms according to the movement of the rigid body (315).

[0180] Meanwhile, as seen in FIG. 8, the exterior of the rigid body (315) may be cubic in shape. However, the exterior of the rigid body (315) is not limited to a cubic shape.

[0181] The rigid body (315) may include two sides that can be connected to a mechanical mechanism for moving the rigid body (315), which is a component of the droplet generating device, and a lower surface that allows a plurality of pressure application ports (310) to be fluidly connected to the droplet generating cartridge (100).

[0182] Additionally, among the multiple surfaces of the rigid body (315), at least one pump connection port (324) may be disposed on one surface (e.g., rear, side, front, top, or bottom). For example, it may be disposed on the remaining surfaces excluding the two sides to which the mechanical mechanism is connected and the bottom surface where the multiple pressure application ports (310) are formed, or it may be disposed on the two sides or the bottom surface.

[0184] Since the rigid body (315) has a three-dimensional shape including multiple faces, it may be desirable for the second air pipe (322d) to be implemented as a flexible tube so that the rigid body (315) can move smoothly according to the direction (2) and / or direction (3) of FIG. 9. Additionally, it may be desirable for the second air pipe (322d) to be a flexible tube to maintain a fluid connection between the rigid body (315) and the pump (200) regardless of the position of the rigid body (315). However, it is not limited thereto, and as in Example 2, the second air pipe (322d) may be implemented as a length-variable rigid pipe.

[0185] Meanwhile, the exterior of the rigid body (315) can be fabricated from a material having rigidity. In this case, the air pipe network (321) and the first air pipe (322c) inside the rigid body (315) can be created by drilling from one side of the rigid body (315) toward the opposite side. At this time, the air passage does not need to completely penetrate from one side to the opposite side. For example, the air pipe network (321) and the first air pipe (322c) can be formed in the form of a tunnel (or channel) inside the rigid body (315).

[0186] In this case, in order to fluidly connect the air pipe network (321) and the first air pipe (322c) and to place a component such as a valve (323) inside the rigid body (315), a part of the air pipe network (321) and / or a part of the first air pipe (322c) may be formed outside the rigid body (315). This will be described later.

[0188] Meanwhile, when a rigid body (315) composed of multiple surfaces physically contacts a droplet generating cartridge (100) through movement in the direction (3) of FIG. 9, the multiple pressure application ports (310) of the rigid body (315) and the droplet generating cartridge (100) can maintain a more stable fluid coupling due to the pressing force of the rigid body (315). When the multiple pressure application ports (310) and the droplet generating cartridge (100) maintain a stable fluid coupling, the pressure applied to the multiple pressure application ports (310) and the droplet generating cartridge (100) can be stable.

[0189] Accordingly, the material forming the rigid body (315) must have rigidity, and the mass of the rigid body (315) may be able to maintain a stable fluidic bond with the droplet generating cartridge (100). For example, the material forming the rigid body (315) may have rigidity and a density that allows it to maintain a stable fluidic bond with the droplet generating cartridge (100) depending on the volume of the rigid body (315).

[0190] For example, the rigid body (315) can be made using a material with rigidity such as aluminum, alloy steel, steel, nickel alloys, ceramic, tungsten, copper, plastic (e.g., PEEK (Polyether Ether Ketone), PEK (Polyether Ketone), PTFE (Polytetrafluoroethylene)), or stainless steel.

[0192] In addition, the flexible tubes used in Examples 1 to 3 may be produced using a flexible material. For example, the flexible tubes may be produced using materials such as neoprene, silicone, nylon, polyurethane, PVC, or rubber.

[0194] Meanwhile, the rigid pipe used in Examples 1 and 2 can be produced using a material that has rigidity, such as a rigid body (315).

[0196] [Example 4: Droplet generating device for Examples 1 to 3]

[0197] FIGS. 10 and 11 are intended to illustrate an example of a droplet generating device (1000) to which any one of the above-described embodiments 1 to 3 may be applied.

[0198] Referring to FIGS. 10 to 11, the droplet generating device (1000) may include a pump (200), a pressure applying structure (300), a motor (400), a mechanical mechanism (500), a position sensor (600), a power supply (700), and a controller (800).

[0199] The pressure application structure (300) may be any one of the pressure application structures of the above-described embodiments 1 to 3. Therefore, a detailed description of the pressure application structure (300) is omitted. Meanwhile, the valve (323) included in the pressure application structure (300) may be a proportional valve or a solenoid valve. However, it is not limited thereto, and any valve that operates to allow or not allow the pressure applied by the pump to be transmitted to a plurality of pressure application ports (310) may be used as a valve included in the pressure application structure (300) according to any one of embodiments 1 to 3 of the present disclosure.

[0200] The motor (400) is mechanically connected to the mechanical mechanism (500) and can provide mechanical force to at least one mechanical component included in the mechanical mechanism (500) to move the pressure application structure (300) and / or cartridge tray (510a). Here, the mechanical force provided by the motor (400) may be a rotational force. The rotational force provided by the motor (400) is converted into a linear force by the at least one mechanical component, and the converted linear force moves the pressure application structure (300) and / or cartridge tray (510a) in a specific axial direction. At this time, the mechanical component that converts the rotational force of the motor (400) into a linear force is called a force conversion element.

[0201] For example, the linear force converted by the first force conversion element can move the pressure application structure (300) in the y-axis direction (e.g., the up-down direction of the droplet generating device (1000)), and the linear force converted by the second force conversion element can move the cartridge tray (510a) in the x-axis direction (e.g., the front-back direction of the droplet generating device (1000)). At this time, the y-axis may be the up-down direction of the droplet generating device (1000), and the x-axis may be the front-back direction of the droplet generating device (1000). Accordingly, the y-axis may be an axis perpendicular to the x-axis. Meanwhile, the x-axis may be an axis parallel to the surface of the pressure application structure (300) in which a plurality of pressure application ports (310) are formed, and the y-axis may be an axis perpendicular to the surface of the pressure application structure (300) in which a plurality of pressure application ports (310) are formed.

[0202] For example, if a part of the pressure application structure (300) is composed of a rigid body (315) according to Example 3, the x-axis may be parallel to the lower surface of the rigid body (315) on which a plurality of pressure application ports (310) are formed, and the y-axis may be perpendicular to the lower surface.

[0203] Additionally, the x-axis and y-axis of FIG. 11 may be the same as the x-axis and y-axis described in FIG. 4, FIG. 5, FIG. 7, and FIG. 9. In other words, the direction (1) in Examples 1 to 3 may be a unidirectional direction on the x-axis. For example, the direction (1) may be a direction from the outside to the inside of the droplet generating device (1000). Or, for example, the direction (1) may be a direction from the front to the rear of the droplet generating device (1000).

[0204] Additionally, the direction (2) in Examples 1 to 3 may be opposite to one direction on the x-axis. For example, the direction (2) may be a direction from the inside to the outside of the droplet generating device (1000). Or, for example, the direction (2) may be a direction from the rear to the front of the droplet generating device (1000).

[0205] Additionally, the direction (3) in Examples 1 to 3 may be a unidirectional direction on the y-axis. For example, the direction (3) may be a direction from the top surface to the bottom surface of the droplet generating device (1000). Or, for example, the direction (3) may be a direction from the top cover to the bottom plate of the droplet generating device (1000).

[0206] Meanwhile, the number of motors (400) according to the present disclosure may be one, but may be two or more. For example, one motor may provide rotational force to the first force conversion element and the second force conversion element, or the first motor may provide rotational force to the first force conversion element and the second motor may provide rotational force to the second force conversion element.

[0207] The mechanical mechanism (500) may mean a set of mechanical components for moving the pressure application structure (300) along the y-axis and moving the droplet generating cartridge (100) along the x-axis using mechanical force provided from the motor (400).

[0208] The mechanical mechanism (500) may include a droplet generation moving mechanism (510) and a pressure application structure moving mechanism (520). The droplet generation moving mechanism (510) is a set of mechanical components for moving the droplet generation cartridge (100). For example, the droplet generation moving mechanism (510) may include a cartridge tray (510a), a cartridge tray rail (510b), and the second force conversion element (not shown).

[0209] The cartridge tray (510a) provides a plane on which the droplet generating cartridge (100) is placed. For example, the droplet generating cartridge (100) may be placed at a specific location on the upper surface of the cartridge tray (510).

[0210] The cartridge tray rail (510b) provides a path along which the cartridge tray (510a) can move. In other words, the cartridge tray rail (510b) helps the cartridge tray (510a) move stably in the x-axis direction parallel to the rail path provided by the cartridge tray rail (510b).

[0211] As described above, the second force conversion element (not shown) converts the rotational force provided by the motor (400) into a linear force in the x-axis direction to move the cartridge tray (510a). For example, the second force conversion element may be a lever, a screw, or a pulley.

[0212] The pressure-applying structure moving mechanism (530) is a set of mechanical components for moving the pressure-applying structure (300). For example, the pressure-applying structure moving mechanism (520) may include a side support (520a), a pressure-applying structure rail (520b), and the first force conversion element (not shown).

[0213] The side support (520a) includes an inner surface on which a pressure-applying structure rail (520b) is mounted. For example, the side support (520a) may include two supports, each of which is positioned opposite each other. A pressure-applying structure rail (520b) is positioned on the inner surface of each support.

[0214] The pressure application structure rail (520b) is mechanically connected to both sides of the pressure application structure (300) to help the pressure application structure (300) move stably in a specific axial direction. For example, the pressure application structure rail (520b) included on each of the two inner sides of the side support (600) enables the pressure application structure (300) to move stably in the y-axis direction parallel to the rail path provided by the pressure application structure rail (520b). At this time, the pressure application structure rail (520b) may be mechanically connected to both sides of the pressure application structure (300).

[0215] For example, FIG. 12 illustrates the configurations of a rigid body (315) for connecting the rigid body (315) described in Example 3 to a pressure-applying structure rail (520b) and a motor (400). Referring to FIG. 12, the rigid body (315) may further include a rail coupling part (316) that connects the rigid body (315) to a pressure-applying structure rail (520b) that assists in the y-axis movement of the rigid body (315), and a motor coupling part (317) for mechanically connecting the rigid body (315) to the motor (400). In this case, a first force conversion element may be mechanically connected to the motor coupling part (317). In other words, the motor coupling part (317) may be mechanically connected to the motor (400) through the first force conversion element.

[0216] Meanwhile, the pressure application structure (300) described in Examples 1 and 2 may further include a rail coupling part (316) for connecting to a pressure application structure rail (520b) and a motor coupling part (317) for mechanically coupling with a motor (400), similar to the rigid body (315) of Example 3, and may be mechanically coupled with the motor (400) and the pressure application structure rail (520b) according to the description above.

[0217] As described above, the first force conversion element (not shown) converts the rotational force provided by the motor (400) into a linear force in the y-axis direction, thereby moving the pressure application structure (300) in the y-axis direction. For example, the first force conversion element may be a lever, a screw, or a pulley.

[0218] Meanwhile, although not illustrated in FIGS. 10 and 11, the pressure application structure movement mechanism (530) may further include a side support rail and a third force conversion element. The side support rail can move the side support in the x-axis direction, thereby enabling the pressure application structure (300) to move in the x-axis direction. Meanwhile, the third force conversion element converts the rotational force provided from the motor (400) into a linear force in the x-axis direction, thereby providing a force capable of moving the side support (520a) in the x-axis direction. At this time, the third force conversion element may convert the rotational force provided from the first motor (400a) or the second motor (400b) into a linear force, or convert the rotational force provided from a third motor different from the first motor (400a) and the second motor (400b) into a linear force.

[0219] The position sensor (600) can detect the position of the pressure application structure (300) on the y-axis.

[0220] The pump (200) generates pressure. Additionally, the pump (200) is fluidically connected to a pressure application structure (300). The fluid connection between the pump (200) and the pressure application structure (300) allows pressure to be applied to a droplet generating cartridge (100) through a plurality of pressure application ports (310). In the present disclosure, the number of pumps (200) may be one or two or more. Meanwhile, the pump (200) according to an embodiment of the present disclosure may be a diaphragm pump. However, it is not limited thereto, and any pump capable of providing negative or positive pressure to a plurality of pressure application ports (310) may be used as the pump according to an embodiment of the present disclosure.

[0221] The power source (700) can provide power to enable the motor (400), pump (200), valve (323), position sensor (600), and controller (800) to operate. For example, the power source (700) can be electrically connected to each of the motor (400), pump (200), position sensor (700), and controller (800) to provide power.

[0222] Alternatively, for example, the power supply (700) may be electrically connected to the controller (800) to provide power to the controller (800), and power may be provided through the controller (900) to the motor (400), valve (323), pump (200), and position sensor (700) that are electrically connected to the controller (800).

[0223] The controller (800) can control the operation of the valve (323), motor (400), pump (200), and position sensor (600). Referring to FIG. 10, the controller (800) can be electrically connected to the pump (200), motor (400), valve (323), position sensor (600), and power supply (700).

[0224] The controller (800) receives power from the power source (700) and controls the operation of the droplet generating device (1000) described in the present disclosure, and can control the operation of the pump (200), motor (400), valve (323), and position sensor (600) in order to control the operation of the droplet generating device (1000).

[0226] FIG. 13 shows an example in which the pressure application structure (300) of Example 3 is mounted on the droplet generating device (1000) described through FIG. 10 to 11. However, FIG. 12 shows an example in which Example 3 among the above-described Examples 1 to 3 is mounted on the droplet generating device (1000) for the sake of convenience of understanding, and the pressure application structure (300) mounted on the droplet generating device (1000) is not limited to Example 3. That is, it is obvious that the pressure application structure (300) of Examples 1 to 3 can be mounted on the droplet generating device (1000) and moved according to the description of FIG. 10 to 11 described above.

[0227] Referring to FIG. 13, as described above, the air pipe mesh (321) and the first air pipe (322c) inside the rigid body (315) can be created by drilling from one side of the rigid body (315) toward the opposite side. In this case, to fluidly connect the air pipe mesh (321) and the first air pipe (322c) and to place a component such as a valve (323) inside the rigid body (315), a portion of the air pipe mesh (321) and / or a portion of the first air pipe (322c) is shown formed outside the rigid body (315). 322c in FIG. 13(a) is a portion of the first air pipe (322c) formed outside the rigid body (315), and 321 in FIG. 13(b) is a portion of the air pipe mesh (321) formed outside the rigid body (315).

[0229] FIG. 14 is intended to explain the operation process of a droplet generating device (1000).

[0230] The operation process of the droplet generating device (1000) described below should be understood as follows: when a user inputs a command to activate the power supply (700) (e.g., power ON), and the power supply (700) supplies power to the controller (800), the controller (800) controls the pump (200), valve (323), position sensor (600), and motor (400). Therefore, in the description below, the operation of the droplet generating device (1000) should be understood as being performed by the control of the controller (800).

[0231] Referring to FIG. 14, a motor (400) (e.g., a second motor) moves the cartridge tray (510a) out of the droplet generating device (1000) along the x-axis direction of FIG. 11 (S1401). The user places the droplet generating cartridge (100) in a designated area within the cartridge tray (510a) (S1403). At this time, fluid is stored in the fluid reservoir (110) of the droplet generating cartridge (100), PCR reaction solution is stored in the PCR reaction solution reservoir (120) of the droplet generating cartridge (100), and the droplet reservoir (130) of the droplet generating cartridge (100) is empty.

[0232] The motor (400) (e.g., the second motor) moves the cartridge tray (510a) into the interior of the droplet generating device (1000) along the x-axis direction of FIG. 11 (S1405). For example, when the droplet generating device (1000) receives a command to move the cartridge tray (510a) into the interior of the droplet generating device (1000), or when the droplet generating device (1000) detects that the droplet generating device (1000) is placed on the cartridge tray (510a), or when the droplet generating device (1000) (i.e., the controller (800)) counts a preset time after the cartridge tray (510a) has moved outside the droplet generating cartridge (100) and the preset time has elapsed, the motor (400) (e.g., the second motor) moves the cartridge tray (510a) into the interior of the droplet generating device (1000).

[0233] The motor (400) (e.g., the first motor) moves a plurality of pressure application ports (310) or a rigid body (315) to move the plurality of pressure application ports (310) to the upper surface of the droplet generating cartridge (100) (S1407). Accordingly, the plurality of pressure application ports (310) are fluidly connected to the droplet reservoir (113) (when negative pressure is provided) or the PCR reaction solution reservoir (112) and oil reservoir (111) (when positive pressure is provided). Meanwhile, the movement process and operation for the plurality of pressure application ports (310) to move to the upper surface of the droplet generating cartridge (100) and to be fluidly connected to the droplet generating cartridge (100) have already been described in Examples 1 to 3, so they are omitted as redundant descriptions.

[0234] When the droplet generating device (1000) detects through the position sensor (600) that a plurality of pressure application ports (310) or a rigid body (315) has moved to the second position on the y-axis, the motor (400) (e.g., the first motor) stops operation so that the plurality of pressure application ports (310) or the rigid body (315) are fixed to the second position. For example, the controller (900) receives position information of the plurality of pressure application ports (310) or the rigid body (315) from the position sensor (600), and when the received position information indicates that the plurality of pressure application ports (310) or the rigid body (315) has moved to the second position on the y-axis, the motor (400) (e.g., the first motor) stops operation so that the plurality of pressure application ports (310) or the rigid body (315) are fixed to the second position.

[0235] Here, the second position is the same as the second position described in Examples 1 to 3, and is a position that allows a plurality of pressure application ports (310) and a droplet generating cartridge (100) to be fluidly coupled.

[0236] The pump (200) generates pressure (negative pressure or positive pressure). Additionally, when the droplet generating device (1000) opens the valve (323), the pressure generated by the pump (200) is applied to the droplet generating cartridge (100) through a plurality of pressure application ports (310) (S1409).

[0237] For example, the pump (200) can apply negative pressure to the droplet reservoir (130) through a plurality of pressure application ports (310), or apply positive pressure to the oil reservoir (110) and the PCR reaction solution reservoir (120) through a plurality of pressure application ports (310).

[0238] Here, the specific operation process in which the pump (200) generates pressure and the droplet generating device (1000) opens the valve (323) will be described later.

[0239] When pressure generated from the pump (200) is applied to the droplet generating cartridge (1000), as described in FIG. 1, a droplet is generated as the fluid and the PCR reaction solution meet, and the generated droplet is stored in the droplet storage (113) (S1411).

[0241] [Example 5: Method of applying pressure to a droplet generating cartridge (100)]

[0242] In Examples 1 to 3, a pressure application structure (300) capable of stably applying pressure to a droplet generating cartridge (100) was proposed.

[0243] In addition, in the description of S1409 of FIG. 14 described above, it was explained that the pump (200) generates pressure, and as the valve (323) opens, the pressure generated by the pump (200) is applied to the droplet generating cartridge (100) through a plurality of pressure application ports (310).

[0244] Meanwhile, in order for the droplet generating device (1000) to stably apply pressure to the droplet generating cartridge (100), it may be necessary to further control the pump (200) and the valve (323) so that the pressure is stably applied.

[0245] Accordingly, in Example 5, we will examine the control method of the pump (200) and valve (323) for the droplet generating device (1000) to stably apply pressure to the droplet generating cartridge (100). As described above, the control of the pump (200) and valve (323) can be performed by the controller (800) of the droplet generating device (1000).

[0246] FIG. 15 is intended to explain a method of controlling a pump (200) and a valve (323) for stably applying pressure. However, as described above, it is not limited thereto, and even when the pump (200) generates positive pressure, the operation control of the pump (200) and the valve (323) can be performed in the same way.

[0247] As previously described in FIG. 14, when a plurality of pressure application ports (310) or a rigid body (315) moves to the upper surface of the droplet generating cartridge (100) (see S1407), the valve (330) is closed and the pump (200) is turned OFF so that no pressure is generated (Fig. 15(a)).

[0248] When a plurality of pressure application ports (310) or a rigid body (315) is moved to the upper surface of the droplet generating cartridge (100) and the droplet generating cartridge (100) and the plurality of pressure application ports (310) are fluidically coupled, the pump (200) is turned ON at time t0 to generate pressure. However, even at this time, the valve (330) is still closed (Fig. 15(b)). At this time, t0 may be a point in time after a first time has elapsed since the plurality of pressure application ports (310) were fluidly coupled with the droplet generating cartridge (100). For example, the first time may be 0 seconds or several seconds greater than 0.

[0249] At t1, after a second time has elapsed from t0, the valve (323) is opened, and the pressure generated by the pump (200) can be applied to the droplet generating cartridge (100) through a plurality of pressure application ports (310) (Fig. 15(c)). Here, for example, the second time may be several seconds, or a preset time.

[0250] The valve (323) is closed at t2, after a third time has elapsed since t1 (Fig. 15(d)), and can be opened again at t3, after a fourth time has elapsed since t2 (Fig. 15(e)). Additionally, at t4, after a fifth time has elapsed since t3, the valve (323) is closed again, and the pump (200) can stop operating to stop generating pressure (Fig. 15(f)). Here, for example, each of the third to fifth times may be a few seconds and may be a preset time.

[0251] However, the process of FIG. 15 (d) to FIG. 15 (e) may be optional. That is, after proceeding to FIG. 15 (c), FIG. 15 (d) to FIG. 15 (e) may be omitted, and at t2, the valve (323) may be closed and the pump (200) may stop operating to stop producing pressure.

[0252] After t1, the valve (323) is open, and the pump (200) can still generate a constant pressure. If the pump (200) generates negative pressure, the air pipe network (321) between the multiple pressure application ports (310) and the valve (323) can maintain a first atmosphere (e.g., atmospheric pressure) from t0 to t1. Additionally, the second atmosphere in the air pipe (322) between the valve (323) and the pump (200) can decrease as the time progresses from t0 to t1. For example, the second atmosphere in the air pipe (322) can approach a vacuum as the time progresses from t0 to t1. When the valve (323) opens at t1, the pressure in the air pipe network (321) and the pressure in the air pipe (322) reach equilibrium during the time interval between t1 and t2. At this time, the time required for the pressure of the air pipe network (321) and the pressure of the air pipe (322) to reach equilibrium at t1 when the valve (323) is open may be a very short time of less than 2 seconds.

[0253] Meanwhile, by closing the valve (323) again at t2 and having the pump (200) continue to generate pressure, the air pressure in the air pipe (322) can decrease again as it goes from t2 to t3. For example, the air pressure in the air pipe (322) can approach a vacuum as it goes from t2 to t3. When the valve (323) is opened again at t3, the pressure in the air pipe network (321) and the pressure in the air pipe (322) reach equilibrium again. At this time, the pressure in the air pipe network (321) would have been lower than the first pressure due to the negative pressure transmitted between t1 and t2, so it can be reached in a shorter time than the time it took to reach equilibrium between t1 and t2.

[0254] On the other hand, if the pump (200) generates positive pressure, the air pipe network (321) between the multiple pressure application ports (310) and the valve (323) can maintain a first atmosphere (e.g., atmospheric pressure) from t0 to t1. Additionally, the second atmosphere in the air pipe (322) between the valve (323) and the pump (200) can increase from t0 to t1. For example, the second atmosphere in the air pipe (322) can become increasingly greater than the first atmosphere from t0 to t1. When the valve (323) opens at t1, the pressure in the air pipe network (321) and the pressure in the air pipe (322) reach equilibrium during the time interval between t1 and t2. At this time, the time required for the pressure of the air pipe network (321) and the pressure of the air pipe (322) to reach equilibrium at t1 when the valve (323) is open may be a very short time of less than 2 seconds.

[0255] Meanwhile, when the valve (323) is closed again at t2 and the pump (200) continues to generate pressure, the air pressure in the air pipe (322) can increase again as it goes from t2 to t3. Also, when the valve (323) is opened again at t3, the pressure in the air pipe network (321) and the pressure in the air pipe (322) reach equilibrium again. At this time, the pressure in the air pipe network (321) would have become higher than the first atmosphere due to the negative pressure transmitted between t1 and t2, so it can be reached in a shorter time than the time it took to reach equilibrium between t1 and t2.

[0256] Example 5 prevents large fluctuations in vibration and pressure that occur when the pump (200) starts generating pressure (i.e., when the pump (200) is driven) from being transmitted to the droplet generating cartridge (100).

[0257] When the pump (200) starts generating pressure, significant vibration occurs in the pump (200), so a relatively large and unstable pressure may be applied to the droplet generating cartridge (100). However, after a certain amount of time has elapsed since the pump (200) started generating pressure, the operation of the pump (200) becomes stable, the vibration decreases, and a stable pressure may be applied.

[0258] Therefore, if the valve (323) is opened before the operation of the pump (200) stabilizes, pressure may not be stably applied to the droplet generating cartridge (100) before and after the operation of the pump (200) stabilizes, and the size of the generated droplets may not be uniform. In addition, due to the high pressure generated when the pump (200) starts generating pressure, the PCR reaction solution and oil may move too quickly to the droplet storage (113), and droplets may not be properly generated.

[0259] Accordingly, to prevent vibrations and unstable high pressure from being supplied to the droplet generating cartridge (300) when the pump (200) begins to apply pressure, the droplet generating device (1000) keeps the valve (323) closed until t1, and then opens the valve (323) after t1 (i.e., after the operation of the pump (200) has stabilized). This prevents droplets from being generated before the pump (200) has stabilized, so that the size of the droplets can be uniform.

[0261] Hereinafter, experimental examples are described regarding whether the size of the droplet is generated uniformly when each pressure application structure (300) is used, using the pressure application structures (300) designed by the inventors of the present application.

[0263] [Design Example 1]

[0264] The present disclosure describes Design Example 1 with reference to FIG. 16.

[0265] The pump (200) is a diaphragm pump. The negative pressure generated by the diaphragm pump is 0.56 bar.

[0266] Additionally, part (321a) of the air pipe network is a 10mm stainless steel (SUS304) pipe. Additionally, the air pipe (322) is a 15mm stainless steel (SUS304) pipe.

[0267] The valve (323) is a proportional valve. Eight pressure application ports (310) are formed by drilling eight holes in the lower surface of a plastic plate, and the remaining part (321b) of the air pipe network is formed within the plate. Part (321a) and the remaining part (321b) of the air pipe network are connected through a connection port.

[0269] [Design Example 2]

[0270] The present disclosure describes design example 2 with reference to FIG. 16.

[0271] It is identical to Design Example 1 except that part (321a) of the air pipe network is a 15 mm stainless steel (SUS304) pipe.

[0273] [Design Example 3]

[0274] The present disclosure describes design example 3 with reference to FIG. 16.

[0275] It is identical to Design Example 1 except that part (321a) of the air pipe network is a 20mm stainless steel (SUS304) pipe.

[0277] [Design Example 4]

[0278] The present disclosure describes design example 4 with reference to FIG. 16.

[0279] It is identical to Design Example 1 except that the air tube (322a) is a 15 mm flexible urethane tube.

[0281] [Design Example 5]

[0282] The present disclosure describes design example 5 with reference to FIG. 16.

[0283] It is identical to Design Example 1 except that part (321a) of the air pipe mesh is a 15mm stainless steel (SUS304) pipe and the air pipe (322a) is a 15mm flexible urethane tube.

[0285] [Design Example 6]

[0286] The present disclosure describes design example 6 with reference to FIG. 16.

[0287] It is identical to Design Example 1 except that part (321a) of the air pipe mesh is a 20mm stainless steel (SUS304) pipe and the air pipe (322a) is a 15mm flexible urethane tube.

[0289] [Design Example 7]

[0290] The present disclosure describes design example 7 with reference to FIG. 17.

[0291] The pump (200) is a syringe pump. The negative pressure generated by the syringe pump is XX Pa. The rigid body (315) is made of aluminum. Formed inside the rigid body (315), the length of the air pipe network (321) between the pressure application ports and the valve is 61 mm, and the length of the first air pipe (322c) between the valve and the pump connection port is 30 mm.

[0292] The valve (323) is a PP valve (Pilot-Operated Proportional valve). The number of pressure application ports formed on the lower surface of the rigid body (315) is 8. The second air tube (322d) is a 21 mm flexible urethane tube.

[0294] [Comparison Example 1]

[0295] The present disclosure describes Comparative Example 1 with reference to FIG. 16.

[0296] It is identical to Design Example 1 except that part (321a) of the air pipe mesh is a 10mm flexible urethane tube and the air pipe (322a) is a 15mm flexible urethane tube.

[0298] [Comparison Example 2]

[0299] The present disclosure describes Comparative Example 2 with reference to FIG. 16.

[0300] It is identical to Design Example 1 except that part (321a) of the air pipe mesh is a 15mm flexible urethane tube and the air pipe (322a) is a 15mm flexible urethane tube.

[0302] [Comparison Example 3]

[0303] The present disclosure describes Comparative Example 3 with reference to FIG. 16.

[0304] It is identical to Design Example 1 except that part (321a) of the air pipe mesh is a 20mm flexible urethane tube and the air pipe (322a) is a 15mm flexible urethane tube.

[0306] [Experimental Method]

[0307] The experiment was conducted through the following process.

[0308] (1) A mixture of water (DI water) and PCR premix was dispensed into 8 PCR reaction wells of the droplet generating cartridge, and oil was dispensed into 8 oil wells.

[0309] (2) Eight pressure application ports were physically brought into contact with eight droplet reservoirs (Wells) of the droplet generating cartridge.

[0310] (3) Voltage was supplied to the pump through the power source to make the pump generate negative pressure.

[0311] (4) After 10 seconds of supplying voltage to the pump, voltage was supplied to the valve through the power supply to open the valve.

[0312] (5) After opening the valve, the voltage supply to the valve was stopped again after 6 seconds to close the valve. At this time, the voltage supply to the pump was not stopped, and accordingly, the negative pressure generation of the pump continued.

[0313] (6) After closing the valve for 10 seconds, voltage was supplied to the valve again to open the valve.

[0314] (7) After 6 seconds of opening the valve again, the power supply to the pump and the power supply to the valve were stopped.

[0315] (8) The size of the droplets formed in the 8 oil wells was observed under a microscope, and images of the droplets were taken. At this time, the magnification of the images used in each experiment was the same.

[0317] [Experimental Results]

[0318] [1] Experimental results of Design Example 1 (Fig. 18)

[0319] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 113.76 113.54 119.35 118.51 111.67 115.86 115.45 3.02 2.61 Well 2 109.01 106.60 107.13 103.92 105.53 107.16 106.56 1.72 1.61

[0320] [2] Experimental results of Design Example 2 (Fig. 19)

[0321] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 104.16 107.21 105.28 106.41 109.27 106.16 106.42 1.74 1.64 Well 2 105.92 108.14 104.11 105.11 109.21 107.75 106.71 1.97 1.84

[0322] [3] Experimental results of Design Example 3 (Fig. 20)

[0323] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 108.76 114.37 115.44 110.22 106.41 109.21 110.74 3.48 3.14 Well 2 108.26 108.13 107.63 109.46 110.45 108.01 108.66 1.07 0.99

[0324] [4] Experimental results of Design Example 4 (Fig. 21)

[0325] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 109.74 109.64 112.66 111.40 114.84 107.41 110.95 2.61 2.35 Well 2 108.72 108.84 109.90 110.56 106.02 111.29 109.22 1.85 1.70

[0326] [5] Experimental results of Design Example 5 (Fig. 22)

[0327] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 117.01 114.26 111.85 110.57 112.08 112.66 113.07 2.27 2.01 Well 2 115.49 111.14 114.33 108.34 115.52 110.79 112.60 2.95 2.62

[0328] [6] Experimental results of Design Example 6 (Fig. 23)

[0329] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 112.15 112.61 113.11 111.43 115.37 112.72 112.90 1.34 1.19 Well 2 112.70 114.73 118.88 114.23 110.58 118.07 114.87 3.16 2.75

[0330] [7] Experimental results of Design Example 7 (Figs. 24 to 27)

[0331] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 105.73 102.34 103.38 103.47 104.39 106.93 104.37 1.69 1.62 Well 2 104.91 105.95 104.9 102.14 100.84 103.94 103.78 1.93 1.86 Well 3 108.23 102.39 107.88 106.08 105.18 108.03 106.30 2.27 2.14 Well 4 102.05 105.89 103.74 103.47 107.78 106.61 104.92 2.18 2.08 Well 5 107.71 105.89 106.06 105.03 105.62 103.74 105.68 1.30 1.23 Well 6 105.56 107.69 107.69 107.88 107.69 105.89 107.07 1.05 0.98 Well 7 100.4 103.47 103.38 103.07 105.01 105.03 103.39 1.69 1.64 Well 8 109.76 108.65 107.69 105.54 102.39 105.62 106.61 2.65 2.49

[0332] [8] Experimental results of Comparative Example 1 (Fig. 28)

[0333] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 131.38 100.12 119.14 100.22 136.90 134.38 120.36 16.78 13.94 Well 2 103.40 107.30 118.48 132.14 126.19 131.38 119.82 12.28 10.25

[0334] [9] Experimental results of Comparative Example 2 (Fig. 29)

[0335] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 124.92 101.32 137.84 101.80 96.94 131.40 115.70 17.74 15.33 Well 2 127.51 164.55 229.41 116.58 170.82 179.54 164.74 40.36 24.50

[0336]

[10] Experimental results of Comparative Example 3 (Fig. 30)

[0337] Droplet 1 (um) Droplet 2 (um) Droplet 3 (um) Droplet 4 (um) Droplet 5 (um) Droplet 6 (um) Average size Standard deviation CV(%) Well 1 113.66 110.87 111.19 119.16 137.39 115.99 118.04 9.97 8.45 Well 2 135.52 147.05 146.45 126.81 219.84 139.72 152.57 33.80 22.16

[0339] [Analysis of Experimental Results]

[0340] [1] Analysis of experimental results of Design Examples 1 to 6 and Comparative Examples 1 to 3

[0341] Comparing the experimental results of Design Examples 1 to 3, it can be seen that the standard deviation of droplet size does not decrease as the length of the stainless steel pipe between the eight pressure application ports and the valve decreases, nor does the standard deviation of droplet size increase as the length of the stainless steel pipe increases. In other words, it appears that there is no correlation between the length of the stainless steel pipe and the uniformity of droplet size.

[0342] This is also true when comparing the experimental results of Design Examples 4 to 6. That is, the length of the stainless steel pipe does not affect the uniformity of droplet size. The same is true when comparing the experimental results of Comparative Examples 1 to 3. The length of the urethane tube does not affect the uniformity of droplet size.

[0343] Accordingly, it can be seen that the length of the pipe or tube between the pressure application ports and the valve does not affect the droplet size.

[0345] [2] Comparative analysis of experimental results between Design Examples 1 to 3 and Comparative Examples 1 to 3

[0346] When comparing the experimental results of Design Examples 1 to 3 with Comparative Examples 1 to 3, it can be seen that the standard deviation of the droplet size generated when the space between the pressure application ports and the pump is a stainless steel pipe is significantly smaller than the standard deviation of the droplet size generated when the space between the pressure application ports and the pump is a urethane tube. That is, in Comparative Examples 1 to 3, the standard deviation of the droplet size was approximately 10 to 40, while in Design Examples 1 to 3, the standard deviation of the droplet size was approximately 1 to 3.

[0347] This means that when the distance between the pressure application ports and the pump is a stainless steel pipe, the standard deviation of the droplet size is smaller in absolute value than when the distance between the pressure application ports and the pump is a urethane tube, and the range of possible standard deviations is also smaller.

[0348] This indicates that when the pressure application ports and the pump are stainless steel pipes, the size of the generated droplets is constant, and the probability of non-uniform droplet size generation is much lower.

[0349] Therefore, it was found that using stainless steel pipes between the pressure application ports and the pump can generate droplet sizes more stably and uniformly than using urethane tubes.

[0351] [3] Comparative analysis of experimental results between Design Examples 3 to 6 and Comparative Examples 1 to 3

[0352] Even when only some of the paths between the pressure application ports and the pump (i.e., the path between the pressure application ports and the valve) were constructed with stainless steel pipes and the remaining paths were constructed with urethane tubes, the standard deviation of the generated droplet size was about 1 to 3. This is much lower than the standard deviation of about 10 to 40 for the generated droplet size when all of the paths between the pressure application ports and the pump were constructed with urethane tubes.

[0353] In other words, it can be seen that even if only some of the paths between the pressure application ports and the pump are made of stainless steel pipes and the remaining paths are made of urethane tubes, droplet sizes can be generated more uniformly than if the entire path between the pressure application ports and the pump is made of urethane tubes.

[0355] [4] Comparative analysis of experimental results of Design Examples 1 to 3 and Design Examples 4 to 6

[0356] When droplets were generated according to Design Examples 1 to 3, the standard deviation of the droplet size was approximately 1 to 3, and when droplets were generated according to Design Examples 4 to 6, the standard deviation of the droplet size was also approximately 1 to 3. In other words, the standard deviation of the droplet size of Design Examples 1 to 3 and the standard deviation of the droplet size of Design Examples 4 to 6 are judged to be almost similar without a significant difference.

[0357] Accordingly, it was found that droplets can be generated sufficiently uniformly even if only some of the paths between the pressure application ports and the pump are constructed of stainless steel pipes and the remaining paths are constructed of urethane tubes, and it is not necessary to construct all paths of stainless steel pipes.

[0358] In particular, it can be seen that if some of the paths between the pressure application ports and the pump that are located closer to the pressure application ports than the pump (i.e., at least some of the paths between the pressure application ports and the valve) are constructed of stainless steel pipes, the droplet size can be made uniform.

[0359] Meanwhile, if some of the paths between the pressure application ports and the pump that are located closer to the pump than the pressure application ports (i.e., at least some of the paths between the valve and the pump) are constructed of urethane tubes, it may be more helpful in facilitating the movement of multiple pressure application ports.

[0360] Therefore, considering the mobility of multiple pressure application ports and the uniformity of the generated droplet size, it is considered desirable to configure some of the paths between the pressure application ports and the pump that are closer to the pressure application ports than the pump with rigid pipes, and the remaining paths with flexible tubes.

[0362] [5] Comparative analysis of experimental results between Design Example 7 and Comparative Examples 1 to 3

[0363] When droplets were generated according to Design Example 7, the standard deviation of the droplet size was approximately 1 to 2.5, and when droplets were generated according to Comparative Examples 1 to 3, the standard deviation of the droplet size was approximately 10 to 40.

[0364] It can be seen that when a droplet is generated using a rigid aluminum body according to Design Example 7, the standard deviation of the droplet size is much smaller than when a droplet is generated according to Comparative Examples 1 to 3.

[0365] In other words, it can be seen that using a rigid body to generate droplets allows for the creation of much more uniform droplet sizes than configuring the path between the pressure application ports and the pump with a urethane tube.

[0367] [6] Comparative analysis of experimental results between Design Example 7 and Design Examples 1 to 6

[0368] When droplets were generated according to Design Example 7, the standard deviation of the droplet size was approximately 1 to 2.5, and when droplets were generated according to Design Examples 1 to 6, the standard deviation of the droplet size was approximately 1 to 3.

[0369] In particular, it was found that the standard deviation of each well in Design Example 7 was more uniform than the standard deviation of each well in Design Examples 1 to 6.

[0370] In other words, it can be seen that the size of the generated droplets is more uniform when a rigid body is used as in Design Example 7 compared to when at least part of the path between the pressure application ports and the pump is used as a rigid pipe.

[0371] This is because the mass of the rigid body is greater than the mass of the rigid pipe, and in Design Example 7, pressure application ports are formed inside the rigid body, so the force with which the pressure application ports press the droplet generating cartridge is greater in Design Example 7 than in Design Examples 1 to 6.

[0373] Although the embodiments have been described above with reference to limited examples and drawings, those skilled in the art can make various modifications and variations from the description above. For example, suitable results can be achieved even if the described techniques are performed in a different order than described, and / or the components of the described system, structure, device, circuit, etc. are combined or assembled in a form different from described, or replaced or substituted by other components or equivalents.

[0374] Therefore, other implementations, other embodiments, and equivalents to the claims also fall within the scope of the claims set forth below. Explanation of the symbols

[0375] 100: Droplet generating cartridge 200: Pump 300: Pressure application structure 400: Motor 500: Mechanical mechanism 600: Position sensor 700: Power supply 800: Controller 1000: Droplet generating device

Claims

Claim 1 A droplet generating device for providing hydraulic pressure to a droplet generating cartridge storing a prepared PCR reaction solution and oil so that a droplet can be generated within the droplet generating cartridge, comprising: a pump providing hydraulic pressure; a movable rigid body having a cubic shaped body and comprising a plurality of pressure applying ports and at least one pump connecting port, wherein the plurality of pressure applying ports and the at least one pump connecting port are formed on the surface of the movable rigid body, and the movable rigid body further comprises an airway network connecting the plurality of pressure applying ports and the at least one pump connecting port, wherein the airway network is formed inside the movable rigid body; a flexible tube connecting the pump and the at least one pump connecting port; and a motor providing mechanical force. A droplet generating device comprising: a mechanical mechanism for moving the movable rigid body along a first axis using mechanical force provided from the motor; wherein the flexibility of the flexible tube ensures that a fluid connection between the pump and at least one pump connection port is maintained regardless of the position of the movable rigid body changing along the first axis; and wherein the droplet generating cartridge is loaded within the droplet generating device and the ports of the droplet generating cartridge and a plurality of pressure application ports of the movable rigid body are fluidly connected by the movement of the movable rigid body, and the rigidity of the air passage network ensures that hydraulic pressure provided by the pump can be stably applied to the droplet generating cartridge. Claim 2 A droplet generating device according to claim 1, wherein the droplet generating cartridge comprises a plurality of PCR reaction solution reservoirs into which PCR reaction solution is dispensed, a plurality of oil reservoirs into which oil is dispensed, and the plurality of droplet generating reservoirs, wherein hydraulic pressure stably applied to the plurality of droplet generating reservoirs causes the PCR reaction solutions discharged from the plurality of PCR reaction solution reservoirs and the oils discharged from the plurality of oil reservoirs to meet in the plurality of droplet generating reservoirs so that the size of the droplets generated is constant. Claim 3 A droplet generating device according to claim 1, wherein the plurality of pressure application ports are located on the lower surface of the movable rigid body so as to apply hydraulic pressure to the plurality of droplet generating reservoirs. Claim 4 In claim 1, the first axis is a droplet generating device perpendicular to a surface where the plurality of pressure application ports are formed. Claim 5 A droplet generating device according to claim 1, wherein the movable rigid body further comprises a valve that allows hydraulic pressure provided from the pump to be applied to the plurality of droplet generating reservoirs, and the air passage network comprises an air conduit network connecting the valve and the plurality of pressure application ports and an air conduit connecting the valve and the at least one pump connection port. Claim 6 In claim 5, the droplet generating device further comprises a controller that controls the operation of the pump and the valve; wherein the controller controls the pump to start providing the hydraulic pressure at a first time point, and opens the valve to apply the hydraulic pressure provided from the pump to the plurality of droplet generating reservoirs after a first time interval from the first time point. Claim 7 In claim 6, the first time interval is a pre-set droplet generating device. Claim 8 A droplet generating device according to claim 1, further comprising: a position sensor for sensing the position of the movable rigid body; and a controller for controlling the motor, wherein the controller controls the motor based on the sensing of the position sensor so that the plurality of pressure application ports can be fluidly connected to the plurality of droplet generating reservoirs, thereby causing the mechanical mechanism to move the movable rigid body downward along the first axis. Claim 9 A droplet generating device according to claim 1, further comprising: a position sensor for sensing the position of the movable rigid body; and a controller for controlling the mechanical mechanism, wherein the controller controls the motor based on the sensing of the position sensor so that the fluid connection between the plurality of pressure application ports and the plurality of droplet generating reservoirs is released, thereby causing the mechanical mechanism to move the movable rigid body upward along the first axis.

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