Metering mechanism and synthesizing apparatus

Abstract

To accurately meter a liquid without using a conventional outer container.SOLUTION: A metering mechanism 15 comprises: a metering container 7 having a closed internal space 37 in which a liquid L is stored; a measuring instrument 26 for measuring the metering container 7; and an inlet pipe 20 connected from an upstream device to the metering container 7 to supply the liquid L into the internal space 37. The inlet pipe 20 has an extra-length portion 50 that is elastically deformable.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present disclosure relates to a synthesizer for chemically synthesizing proteins, peptides, nucleic acids, etc., and a metering mechanism included in the synthesizer. [Background technology]

[0002] One method for chemically synthesizing proteins, peptides, nucleic acids, etc. involves sequentially supplying multiple types of liquids (reagents) to a reaction vessel and allowing the reaction to proceed in the reaction vessel. For example, when synthesizing nucleic acids, a large number of granular carriers (beads) are placed in the reaction vessel, and while sequentially supplying liquids to the reaction vessel, detritylation, coupling, oxidation, and capping processes are repeatedly carried out, thereby binding bases one after another from the carriers.

[0003] Dozens of different liquids may be used, and these liquids are selectively sent to reaction vessels to produce synthetic products (e.g., nucleic acids) from the molecular materials contained in the liquids. Patent Document 1, for example, describes a known device for performing such chemical synthesis. Patent Document 1 discloses a metering mechanism used in such a synthesis device. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2018-167161 Summary of the Invention [Problem to be solved by the invention]

[0005] In the case of the synthesis apparatus disclosed in Patent Document 1, as shown in Fig. 5, a weighing mechanism 90 has a weighing container 91, a measuring instrument 92, an outer container 93, and a plurality of outlet pipes 95. The weighing container 91 is a container that stores liquid L and has an open top. The measuring instrument 92 has a load sensor (load cell) for weighing the weighing container 91. The outlet pipe 95 is a pipe for sending liquid L stored in a storage container 99 to the weighing container 91.

[0006] Since the weight of the measuring vessel 91 is known, the weight of the liquid L accumulated in the measuring vessel 91 is obtained by measuring the weight of the measuring vessel 91 with the measuring instrument 92. The measured liquid L is sent to the downstream reaction vessel 96, and chemical synthesis using the liquid L is carried out in the reaction vessel 96. In order to prevent excess or deficiency of the liquid L used in the chemical synthesis, it is desirable that the measuring mechanism 90 measure as accurately as possible.

[0007] Therefore, in the case of a conventional measuring mechanism 90, multiple outlet pipes 95 are integrated and these outlet pipes 95 are in a state of non-contact with the measuring container 91. Although tension may act on the outlet pipes 95, the non-contact configuration prevents the influence of this tension from being exerted on the measuring instrument 92 (load sensor). As a result, it becomes possible to accurately measure the liquid L.

[0008] The outer container 93 is required to pump the liquid L in the measuring container 91, which is open at the top. That is, the outer container 93 has a closed storage space 94 therein, and the measuring container 91 is provided in the storage space 94. By supplying gas to the storage space 94, the pressure of the gas acts on the liquid L in the measuring container 91, which is open at the top. The liquid L is pumped into the reaction container 96 by the pressure of the gas.

[0009] As shown in FIG. 5, when an outer container 93 is used, the installation space becomes larger. Therefore, the present disclosure aims to provide a measuring mechanism that has a new technical means that does not use a conventional outer container and that is capable of accurately measuring liquid, and a synthesis apparatus that has such a measuring mechanism. [Means for solving the problem]

[0010] The weighing mechanism of the present invention comprises a weighing container having a closed internal space for storing liquid, a measuring instrument for measuring the weighing container, and an inlet pipe that connects to the weighing container from an upstream device and sends liquid to the internal space, the inlet pipe having an excess length that is elastically deformable.

[0011] The synthesis apparatus of the present invention is a synthesis apparatus for chemical synthesis by selectively sending multiple types of liquid, and includes a liquid delivery means for sending the liquid from each of multiple storage containers containing multiple types of liquid, a measuring mechanism for measuring the liquid sent by the liquid delivery means, and a reaction container in which the liquid measured by the measuring mechanism is placed and a synthetic product is produced, and the measuring mechanism includes a measuring container having a closed internal space and in which the liquid is stored, a measuring instrument for measuring the measuring container, and an inlet pipe that connects to the measuring container from an upstream device included in the liquid delivery means and introduces the liquid into the internal space, and the inlet pipe has an elastically deformable excess length portion. [Effects of the Invention]

[0012] According to the invention of the present disclosure, the measuring mechanism does not require a conventional outer container and can accurately measure liquid. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a configuration diagram showing an example of a synthesis device equipped with a metering mechanism. [Figure 2] FIG. 2 is an explanatory diagram of the weighing mechanism. [Figure 3] FIG. 3 is an explanatory diagram showing a modified example of the extra length portion. [Figure 4] FIG. 4 is an explanatory diagram showing a modified example of the synthesis device. [Figure 5] FIG. 5 is an explanatory diagram of a conventional synthesis device. DETAILED DESCRIPTION OF THE INVENTION

[0014] <Outline of the embodiment of the present invention> Hereinafter, an outline of an embodiment of the present invention will be listed and described. (1) A weighing mechanism according to an embodiment of the present invention comprises a weighing container having a closed internal space for storing liquid, a measuring instrument for measuring the weighing container, and an inlet pipe that connects an upstream device to the weighing container and sends liquid to the internal space, the inlet pipe having an excess length that is elastically deformable.

[0015] In the measuring mechanism having the above configuration, the inlet pipe that introduces the liquid into the internal space of the measuring container is directly connected to the measuring container, and even if tension is applied to the inlet pipe, the excess length prevents the influence of the tension from affecting the measurement in the measuring container, thereby enabling the liquid to be accurately measured. Since the measuring container has a closed internal space, gas can be supplied to the measuring container to pump the liquid in the measuring container to downstream equipment, eliminating the need for an outer container to house the measuring container as in the past.

[0016] (2) The excess length is located in a portion of the inlet pipe that is connected to the upper wall of the measuring container in a hanging state. Even if tension acts on the portion of the inlet pipe that is hanging down and connected to the upper wall of the measuring container, it is possible to prevent the influence of that tension from affecting the measurement of the measuring container.

[0017] (3) In the weighing mechanism of (1) or (2), the excess length portion has a linear shape along a spiral centered on an axis in the vertical direction. In this case, the extent of the excess length is limited and the excess length is not free to elastically deform so as to expand horizontally, which makes it possible to prevent one excess length from coming into contact with the adjacent excess length or the inlet pipe.

[0018] (4) In any one of the weighing mechanisms (1) to (3), a plurality of the inlet pipes are connected to the weighing container, and among the plurality of inlet pipes, the excess length of a first inlet pipe and the excess length of a second inlet pipe located adjacent to the first inlet pipe are arranged at different heights. In this case, even if multiple inlet pipes are arranged close to each other, it is possible to prevent adjacent excess length portions from coming into contact with each other. By arranging multiple inlet pipes close to each other, it is possible to make the metering mechanism more compact.

[0019] (5) Any one of the metering mechanisms (1) to (4) has a guide that supports a portion of the inlet pipe between the upstream device and the excess length portion. The guide makes it possible to prevent contact between adjacent inlet pipes and between adjacent excess length portions.

[0020] (6) Any one of the metering mechanisms (1) to (5) has an exhaust pipe connected to the metering container to discharge gas from the internal space when the liquid is supplied to the metering container through the inlet pipe, and the exhaust pipe has an excess portion that is elastically deformable. In this case, when liquid is supplied to the measuring container through the inlet pipe, gas in the internal space of the measuring container is discharged, and a dedicated discharge pipe is provided for this discharge. Even if tension acts on the discharge pipe, it is possible to prevent the influence of this tension from affecting the measurement of the measuring container.

[0021] (7) Any one of the metering mechanisms (1) to (6) has a downstream pipe connected to the metering container to send liquid to equipment downstream of the metering container, and a gas pipe to supply gas to the internal space to send the liquid from the metering container through the downstream pipe, and the gas pipe has an excess portion that is elastically deformable. When sending the liquid measured in the measuring vessel to a downstream device, gas is supplied to the internal space of the measuring vessel through the gas piping. Even if tension acts on the gas piping, it is possible to prevent the influence of that tension from affecting the measurement in the measuring vessel.

[0022] (8) A synthesis apparatus according to an embodiment of the present invention is a synthesis apparatus for chemical synthesis by selectively sending multiple types of liquids, and includes a liquid delivery means for delivering the liquids from multiple storage containers each containing multiple types of liquid, a measuring mechanism for measuring the liquids delivered by the liquid delivery means, and a reaction container in which the liquid measured by the measuring mechanism is placed and a synthetic product is produced, and the measuring mechanism includes a measuring container having a closed internal space in which the liquids are stored, a measuring instrument for measuring the measuring container, and an inlet pipe that connects to the measuring container from an upstream device included in the liquid delivery means and introduces the liquid into the internal space, and the inlet pipe has an elastically deformable excess length.

[0023] In the synthesis apparatus having the above configuration, the inlet pipe that introduces the liquid into the internal space of the measuring vessel in the metering mechanism is directly connected to the measuring vessel, and even if tension is applied to the inlet pipe, the excess length of the inlet pipe makes it possible to suppress the influence of the tension on the measurement in the measuring vessel. As a result, the liquid can be accurately metered, and a synthesis product can be produced in the reaction vessel using just the right amount of liquid. Since the measuring container has a closed internal space, gas can be supplied to the measuring container to pump the liquid in the measuring container to downstream equipment, eliminating the need for an outer container to house the measuring container as in the past.

[0024] (9) In the synthesis device of (8), the metering mechanism includes a first metering container, a second metering container, a first measuring instrument for measuring the first metering container, and a second measuring instrument for measuring the second metering container, and includes a first inlet pipe that connects the upstream equipment to the first metering container and introduces liquid into the internal space, and a second inlet pipe that connects the upstream equipment to the second metering container and introduces liquid into the internal space, wherein the first inlet pipe has an elastically deformable excess portion, and the second inlet pipe has an elastically deformable excess portion.

[0025] In some cases where it is undesirable for the first and second liquids to mix in the metering mechanism, a first metering container is used to measure the first liquid and a second metering container, separate from the first metering container, is used to measure the second liquid.

[0026] <Details of the embodiment of the present invention> Hereinafter, the details of the embodiments of the present invention will be described. [Overall configuration of the synthesis apparatus] 1 is a structural diagram showing an example of a synthesizer equipped with a metering mechanism. The synthesizer is an apparatus that exchanges and reacts multiple types of liquids (solutions). The synthesizer 3 of this embodiment is an apparatus for chemically synthesizing proteins, peptides, nucleic acids, etc., and sequentially supplies multiple types of liquids L (reagents) to a reaction vessel 9, and chemical synthesis proceeds within this reaction vessel 9.

[0027] When synthesizing nucleic acids, a large number of granular carriers (beads) are placed in a reaction vessel 9, and while liquid L is sequentially supplied to this reaction vessel 9, detritylation, coupling, oxidation, and capping processes are repeatedly performed, and molecular materials such as bases are successively bonded from the carriers. Multiple types of liquid L are selectively sent to the reaction vessel 9, and a synthetic product (nucleic acid) is produced from the molecular materials contained in the liquid L.

[0028] The number of liquids L used varies depending on the product to be chemically synthesized. The synthesis apparatus 3 has an area for providing storage containers (reagent bottles) 2 in the same number or more as the types of liquids L. Each storage container 2 stores a respective liquid L. Note that only three storage containers 2 are shown in FIG. 1, and the other storage containers are omitted. The multiple storage containers 2 include a container for storing a cleaning liquid. Each storage container 2 is a sealed container, but is connected to an inlet pipe 5 and an outlet pipe 6.

[0029] The synthesis apparatus 3 includes a tank 4 for storing pressurized gas, an upstream pipe 10, an inlet pipe 5, an outlet pipe 6, a measuring mechanism 15, a downstream pipe 8, a reaction vessel 9, an outlet pipe 19, and a control device 16 for controlling the opening and closing of each valve.

[0030] The tank 4 is filled with a gas at a higher pressure than the atmosphere, and in the present disclosure, argon gas or nitrogen gas is used as the inert gas. Sterilized gas or air may be used instead of the inert gas. The same number of inlet pipes 5 as the number of storage containers 2 are pipes branching off from a common upstream pipe 10. A regulator (electropneumatic regulator) 11 and a valve 12 are provided in the upstream pipe 10. The upstream pipe 10 is connected to the tank 4. Pressurized gas from the tank 4 is supplied to each storage container 2, and the internal pressure of each storage container 2 is adjusted by the regulator 11. The internal pressure of each storage container 2 is increased by the pressurized gas, and the liquid L from the storage container 2 is pressure-fed through the outlet pipe 6.

[0031] As described above, in this embodiment, the liquid delivery means 24 for delivering the liquid L from each of the multiple storage containers 2, which each store multiple types of liquid L, is a pressure delivery system. The liquid delivery means 24 includes the tank 4, the upstream piping 10, the regulator 11, the valve 12, the inlet pipe 5, and the outlet pipe 6.

[0032] Each outlet pipe 6 has a valve 14. The pipe connected to the downstream side (the measuring container 7 side) of each valve 14 serves as an inlet pipe 20 of the measuring mechanism 15. One outlet pipe 6 is connected to one inlet pipe 20 via one valve 14. By selecting the valves 14 to be opened, a predetermined liquid L can be selectively sent (pressurized) from the liquids L in the plurality of storage containers 2 to the measuring container 7 through the outlet pipe 6 and the inlet pipe 20. The selection of the valves 14 to be opened is performed by the control device 16.

[0033] The measuring mechanism 15 selectively obtains multiple types of liquid L from the storage container 2 and measures the liquid L. The measuring mechanism 15 has a measuring container 7 and measures the liquid L stored in the measuring container 7. The measurement result by the measuring mechanism 15 is transmitted to the control device 16, and the control device 16 controls the opening and closing operation of the valve 14 based on the measurement result. As a result, a specified amount of liquid L is obtained in the measuring container 7.

[0034] A predetermined amount of liquid L is sent to the reaction vessel 9 through the downstream pipe 8. The liquid L measured by the measuring mechanism 15 is placed in the reaction vessel 9, and a compound is produced in the reaction vessel 9. A gas pipe 23 is provided between the tank 4 and a measuring vessel 7 (described later) of the measuring mechanism 15. A second regulator (electropneumatic regulator) 18 is provided in the gas pipe 23. Gas from the tank 4 is supplied to the measuring vessel 7 through the gas pipe 23. This gas causes the liquid L in the measuring vessel 7 to be sent (pressurized) to the reaction vessel 9 through the downstream pipe 8.

[0035] As described above, the synthesis apparatus 3 is an apparatus for chemical synthesis by selectively sending multiple types of liquid L to the reaction vessel 9. The liquid L is selectively sent from at least one of the multiple storage vessels 2 to the measuring vessel 7, and after being measured in this measuring vessel 7, it is sent to the reaction vessel 9. The supply of the liquid L to the reaction vessel 9 is repeatedly performed while changing the type of liquid L, and multiple types of liquid L are supplied to the reaction vessel 9 in sequence, and chemical synthesis proceeds in the reaction vessel 9. After the liquid L passes through the reaction vessel 9, the liquid L is discharged through the discharge pipe 19.

[0036] [Regarding Measuring Mechanism 15] 2 is an explanatory diagram of the metering mechanism 15. The metering mechanism 15 measures the liquid L sent by the liquid sending means 24. In addition to the metering container 7, the metering mechanism 15 has a measuring instrument 26, an inlet pipe 20, an outlet pipe 21, a downstream pipe 22, and a gas pipe 23.

[0037] The liquid L sent by the liquid sending means 24 is stored in the measuring container 7. The measuring container 7 has a cylindrical peripheral wall 71, an upper wall 72 that closes the upper opening of the peripheral wall 71, and a lower wall 73 that closes the lower opening of the peripheral wall 71. The space surrounded by the peripheral wall 71, the upper wall 72, and the lower wall 73 is the internal space 37 of the measuring container 7. The measuring container 7 has a closed internal space 37 inside. The measuring container 7 is an airtight container.

[0038] The measuring instrument 26 measures the weight of the measuring container 7 containing the liquid L. The measuring instrument 26 is configured with a load sensor and measures the weight in the measuring container 7. The measuring instrument 26 of the present disclosure has a strain-type load cell. The measuring instrument 26 is supported by a support member 28 of the weighing mechanism 15. The measuring container 7 is supported by a fixed frame 29 of the weighing mechanism 15 via the support member 28 with the measuring instrument 26 attached.

[0039] The weight of the measuring container 7 and the liquid L stored in the measuring container 7 is received by a measuring instrument (weight sensor) 26. Since the weight of the measuring container 7 is known, the weight of the liquid L stored in the measuring container 7 is obtained by measuring the weight of the measuring container 7 with the measuring instrument 26. The measuring device 26 may be configured to have other types of sensors, such as an electromagnetic, piezoelectric, capacitance, magnetostrictive, or gyro load cell.

[0040] As shown in Figure 2, a plurality of inlet pipes 20 are connected to the weighing container 7. In this embodiment, the number of inlet pipes 20 is the same as the number of storage containers 2 (see Figure 1). For ease of explanation, Figure 2 shows the plurality of inlet pipes 20 arranged in a row. In reality, the upper wall 72 of the weighing container 7 is disk-shaped, and the plurality of inlet pipes 20 are connected to the upper wall 72 in a dispersed arrangement, for example, in a grid, staggered, or radial pattern.

[0041] The inlet pipe 20 is connected to the metering container 7 from the valve 14, which is a device upstream of the inlet pipe 20, and sends the liquid L to the internal space 37. The inlet pipe 20 is connected to the top of the metering container 7, and more specifically, to the top wall 72 of the metering container 7. The inlet pipe 20 may be fixed to the top wall 72. The inlet pipe 20 is made of a flexible and elastic tube, for example, a tube made of a resin such as a fluororesin.

[0042] Each of the plurality of inlet pipes 20 has an elastically deformable excess length portion 50. The excess length portion 50 is located in a portion of the inlet pipe 20 that is connected to the upper wall 72 of the measuring container 7 in a hanging state. In this embodiment, the weighing mechanism 15 has a guide 25. The guide 25 is attached to a frame (not shown) of the weighing mechanism 15. The guide 25 is, for example, a flat plate-shaped member. A plurality of inlet pipes 20 pass through the guide 25. The guide 25 supports the plurality of inlet pipes 20 with a gap between them. The guide 25 functions as a spacer that positions the plurality of inlet pipes 20.

[0043] In this embodiment, the excess length portion 50 is located at a portion of the inlet pipe 20 that hangs down from the guide 25 and is connected to the upper wall 72 of the measuring container 7 . The guide 25 may be omitted. In this case, the valve 14 is disposed above the measuring container 7, and the excess length 50 is located in the portion of the inlet pipe 20 that hangs down from the valve 14 and is connected to the upper wall 72 of the measuring container 7.

[0044] The excess length portion 50 is formed as a part of the resin inlet pipe 20, and therefore is elastically deformable in terms of material, and since it literally has an excess length portion (a curved portion), the flexibility of the entire shape is increased and it is elastically deformable. The specific shape of the excess length portion 50 will be described later.

[0045] When the liquid L is supplied from each storage container 2 (see FIG. 1) to the measuring container 7 through the inlet pipe 20, gas is discharged from the internal space 37 of the measuring container 7. A dedicated discharge pipe 21 is provided for this discharge. The discharge pipe 21 is connected to the measuring container 7 (upper wall 72). At least a portion of discharge pipe 21 (the portion connected to measuring container 7) is made of a flexible and elastic tube, similar to inlet pipe 20. Discharge pipe 21 is provided in a hanging state alongside inlet pipe 20. Discharge pipe 21 is also supported by guide 25.

[0046] The discharge pipe 21 has an elastically deformable excess length portion 51. In the present embodiment, the excess length portion 51 is located in a portion of the discharge pipe 21 that is connected to the upper wall 72 of the measuring container 7 in a hanging state. The excess length portion 51 of the discharge pipe 21 may have the same configuration as the excess length portion 50 of the inlet pipe 20. Since the excess length portion 51 is configured as part of the discharge pipe 21, which is made of resin, the material is elastically deformable, and the shape as a whole has increased flexibility and is elastically deformable.

[0047] As described above, the means for sending the liquid L measured in the measuring container 7 to the reaction container 9, which is a downstream device, is also pressure-feeding by gas. That is, when the measured liquid L is sent to the reaction container 9, gas from the tank 4 (see FIG. 1) is supplied to the internal space 37 of the measuring container 7 through the gas piping 23. The gas piping 23 is connected to the tank 4 on its upstream side, and the gas from the tank 4 is supplied to the internal space 37. The liquid L is sent to the reaction container 9 by the pressure of the gas supplied to the internal space 37. In this way, the gas piping 23 is a piping for supplying the gas in the tank 4 to the internal space 37 in order to send out the liquid L in the measuring container 7 through the downstream pipe 22.

[0048] At least the downstream portion of the gas pipe 23 is made of a flexible and elastic tube, similar to the inlet pipe 20. The gas pipe 23 is provided in a hanging state alongside the inlet pipe 20. The gas pipe 23 is also supported by a guide 25. The gas pipe 23 has an elastically deformable excess length portion 52. In the present embodiment, the excess length portion 52 is located in a portion of the gas pipe 23 that is connected to the upper wall 72 of the metering container 7 in a hanging state.

[0049] The excess length portion 52 of the gas pipe 23 may have the same configuration as the excess length portion 50 of the inlet pipe 20. Since the excess length portion 52 is configured as a part of the gas pipe 23 made of resin, the excess length portion 52 is elastically deformable in terms of material, and is also elastically deformable due to increased flexibility in terms of shape as a whole.

[0050] The liquid L measured in the measuring vessel 7 is sent to the reaction vessel 9 through the downstream pipe 22. The downstream pipe 22 is a pipe connected to the measuring vessel 7 in order to send the liquid L to the reaction vessel 9, which is a device downstream of the measuring vessel 7. A valve 36 is provided in the downstream pipe 22. When the liquid L in the storage vessel 2 (see FIG. 1) is sent to the measuring vessel 7, the valve 36 is closed. When a predetermined amount of the liquid L is measured in the measuring vessel 7, the valve 36 is opened, and the liquid L passes through the downstream pipe 22 and is sent to the reaction vessel 9.

[0051] The downstream pipe 22 is made of a flexible and elastic tube at least in its upstream portion, similar to the inlet pipe 20. The downstream pipe 22 is provided in a state of hanging down from the measuring container 7. The downstream pipe 22 has an elastically deformable excess length portion 53. In the present embodiment, the excess length portion 53 is located in a portion of the downstream pipe 22 that hangs down from the bottom wall 73 of the measuring container 7 and is connected to the bottom wall 73.

[0052] The excess length portion 53 of the downstream pipe 22 may have the same configuration as the excess length portion 50 of the inlet pipe 20. Because the excess length portion 53 is configured as part of the downstream pipe 22, which is made of resin, the material is elastically deformable, and the shape as a whole has increased flexibility and is elastically deformable.

[0053] [Regarding the excess length of each pipe] As shown in the enlarged view of Figure 2, the excess length portion 50 of the inlet pipe 20 extends from the upper portion 201 extending in the vertical direction of the inlet pipe 20, has a horizontal component, makes a U-turn, and has a shape that connects to the lower portion 202 extending in the vertical direction of the inlet pipe 20.

[0054] The excess length portion 50 has a curved shape to allow for relative vertical displacement of the upper portion 201 and the lower portion 202 of the inlet pipe 20 due to an external force. That is, for example, when the liquid L is supplied to the measuring container 7, the weight of the liquid may cause the measuring container 7 to slightly displace downward. Even if tension acts on the lower portion 202, which is displaced downward by the measuring container 7, the excess length portion 50 is configured to elastically deform, thereby preventing the upper portion 201 from being displaced by the lower portion 202.

[0055] The excess length portion 50 can prevent the tension acting on the lower portion 202 from being transmitted to the upper portion 201. Similarly, when tension acts on the upper portion 201, the excess length portion 50 can prevent the tension acting on the upper portion 201 from being transmitted to the lower portion 202.

[0056] The inlet pipe 20 is directly connected to the measuring container 7 (upper wall 72), but since the inlet pipe 20 has the excess length 50, even if tension is applied, it is possible to suppress the influence of the tension on the measurement in the measuring container 7. As a result, the measuring mechanism 15 can accurately measure the liquid L.

[0057] FIG. 3 is an explanatory diagram showing a modified example of the excess length portion 50. The excess length portion 50 shown in FIG. 3 has a spiral shape centered on the vertical axis C. The excess length portion 50 is coil-shaped. This excess length portion 50 is freely elastically deformable in the vertical direction. Note that the excess length portion 50 only needs to have a spiral shape as described above, and the number of turns may be multiple as shown in FIG. 3, or may be one.

[0058] Because the excess length portion 50 has a linear shape that follows the spiral, the range of the excess length portion 50 is limited, and the excess length portion 50 does not freely elastically deform so as to expand horizontally. The excess length portion 50 can elastically deform greatly in the vertical direction, but does not elastically deform so as to expand greatly in the horizontal direction. This makes it possible to prevent one excess length portion 50 from contacting the adjacent excess length portion 50 or the inlet pipe 20.

[0059] 2 and 3, among the multiple inlet pipes 20, the excess length portion 50 of a first inlet pipe 20 and the excess length portion 50 of a second inlet pipe 20 located adjacent to the first inlet pipe 20 are arranged at different heights. In the configuration shown in FIGS. 2 and 3, one excess length portion 50 and another adjacent excess length portion 50 are arranged at different heights over the entire length in the vertical direction. Note that one excess length portion 50 and another adjacent excess length portion 50 may be at the same height only for a portion of the vertical direction.

[0060] By making adjacent excess length portions 50 different heights in this way, even if multiple inlet pipes 20 are arranged close to each other, it is possible to prevent contact between adjacent excess length portions 50. By arranging multiple inlet pipes 20 close to each other, it is possible to make the measuring container 7 more compact, and as a result, it is possible to make the measuring mechanism 15 more compact.

[0061] In the embodiment shown in FIG. 2, the metering mechanism 15 has a guide 25 that supports multiple inlet pipes 20. The guide 25 supports the portion of the inlet pipe 20 between the valve 14, which is an upstream device, and the excess length portion 50. The guide 25 prevents the inlet pipe 20 from wobbling. This makes it possible to prevent contact between adjacent inlet pipes 20 and between adjacent excess length portions 50.

[0062] It is possible to prevent the influence of the multiple excess length portions 50 interfering with each other from affecting the measurement of the measuring container 7.

[0063] As described above, the excess length portion 51 of the discharge pipe 21 may have the same configuration as the excess length portion 50 of the inlet pipe 20. With the excess length portion 51, even if tension acts on the discharge pipe 21, it is possible to prevent the influence of the tension from affecting the measurement of the measuring container 7.

[0064] As described above, the excess length portion 52 of the gas piping 23 may have the same configuration as the excess length portion 50 of the inlet pipe 20. The excess length portion 52 makes it possible to prevent the influence of tension acting on the gas piping 23 from affecting the measurement of the measuring container 7.

[0065] As described above, the excess length portion 53 of the downstream pipe 22 may have the same configuration as the excess length portion 50 of the inlet pipe 20. When the liquid L is supplied to the measuring container 7, the weight of the liquid L causes the measuring container 7 to displace downward. Even if the upper portion 221 of the downstream pipe 22 is displaced downward by the measuring container 7, the excess length portion 53 is elastically deformed. This makes it possible to suppress the reaction force from the downstream pipe 22 being applied to the measuring container 7. This enables the measuring mechanism 15 to accurately measure the liquid L.

[0066] [Modification of synthesis device 3] FIG. 4 is an explanatory diagram showing a modified example of the synthesis device 3. In the case of the synthesis apparatus 3 shown in Figures 1 and 2, all of the multiple pipes (outlet pipes 6 and inlet pipes 20) connected to the multiple storage containers 2 are consolidated and measured using a single (common) measuring container 7.

[0067] In the case of the synthesis device 3 shown in Figure 4, multiple storage containers 2 are grouped, and a measuring container 7A and a measuring instrument 26A are used to measure the liquid L in the storage containers 2 included in one group, and a measuring container 7B and a measuring instrument 26B are used to measure the liquid L in the storage containers 2 included in another group. That is, the weighing mechanism 15 has a first weighing container 7A for one group and a first measuring instrument 26A for weighing the first weighing container 7A, and a second weighing container 7B for another group and a second measuring instrument 26B for weighing the second weighing container 7B.

[0068] Additionally, the metering mechanism 15 has a first inlet pipe 20A for one group and a second inlet pipe 20B for the other group. The first inlet pipe 20A is connected from the valve 14, which is an upstream device, to the first measuring container 7A and introduces the liquid L into the internal space 37. The second inlet pipe 20B is connected from the valve 14, which is an upstream device, to the second measuring container 7B and introduces the liquid L into the internal space 37.

[0069] This configuration will be described in detail. The synthesizing apparatus 3 of this embodiment is an apparatus for synthesizing and producing nucleic acids. For this synthesis, a large number of granular carriers (beads) are provided in a reaction vessel 9. While the liquid L from the storage vessel 2 is sequentially supplied to the reaction vessel 9, detritylation, coupling, oxidation, and capping processes are repeatedly performed, and bases are sequentially bound from the carriers.

[0070] An oxidizing liquid is used for the oxidation process. It may be undesirable for the oxidizing liquid and the liquids used in other processes (detritylation, coupling, and capping) to come into contact (mix) in the measuring vessel 7. Therefore, as shown in FIG. 4, the storage vessel 2 containing the oxidizing liquid is included in one group, and the other storage vessels 2 are included in another group. That is, the measuring vessel 7 connected to the storage vessel 2 containing the oxidizing liquid via the outlet pipe 6 and the inlet pipe 20A is referred to as the first measuring vessel 7A. The measuring vessel 7 connected to the storage vessel 2 containing the liquids for other processes (detritylation, coupling, and capping) via the outlet pipe 6 and the inlet pipe 20 is referred to as the second measuring vessel 7B.

[0071] According to the synthesis apparatus 3 shown in Figure 4, a first measuring container 7A is used to measure the first liquid (oxidized liquid), and a second measuring container 7B, which is separate from the first measuring container 7A, is used to measure the second liquid (other liquid).

[0072] The first inlet pipe 20A has an elastically deformable excess length portion 50. The second inlet pipe 20B has an elastically deformable excess length portion 50. The excess length portion 50 of the first inlet pipe 20A and the excess length portion 50 of the second inlet pipe 20B may have the same shape. In the case of the synthesis apparatus 3 shown in FIG. 4, a downstream pipe 8A connected to a first measuring vessel 7A and a downstream pipe 8B connected to a second measuring vessel 7B join together, and synthesis processing is carried out in a single common reaction vessel 9.

[0073] In the configuration shown in Figure 4, the discharge pipe 21 for the first metering container 7A and the gas piping 23 join together at the three-way valve 141. The first common pipe 201 connecting the three-way valve 141 and the first metering container 7A also has an excess length portion 54. The discharge pipe 21 and the gas pipe 23 for the second metering container 7B join together at the three-way valve 142. The second common pipe 202 connecting the three-way valve 142 and the second metering container 7B also has an excess length portion 54. The downstream pipes 8A and 8B also have extra length portions 53.

[0074] The excess length portion 50 of the first inlet pipe 20A, the excess length portion 50 of the second inlet pipe 20B, the excess length portion 54 of the first common pipe 201, the excess length portion 54 of the second common pipe 202, and the excess length portions 53 of the downstream pipes 8A and 8B may each have the same configuration. The extra length portions 50, 53, and 54 shown in FIG. 4 may have a spiral shape centered on the vertical axis, as shown in FIG.

[0075] By dividing the measuring container 7 into measuring container 7A and measuring container 7B, the number of pipes connected to the measuring container 7 can be reduced compared to when all storage containers 2 are connected to one measuring container 7. This reduces the effect of tension on the measuring container 7.

[0076] Note that with regard to the synthesis device 3 shown in Figure 4 and the synthesis device 3 shown in Figures 1 and 2, the same components are assigned the same symbols, and detailed explanations will be omitted, but each component of the synthesis device 3 shown in Figures 1 and 2 can be applied to the synthesis device 3 shown in Figure 4.

[0077] [Configuration of the inlet pipe 20, etc.] As described above (see FIGS. 1 and 4), the storage container 2 for storing a cleaning liquid is included in the multiple storage containers 2. Every time the type of liquid L to be measured by the measuring mechanism 15 is changed, the cleaning liquid may be supplied to the measuring container 7 to perform cleaning. The measuring container 7 has a closed internal space 37. Therefore, the measuring container 7 can be filled with the cleaning liquid, and the entire inner wall surface of the measuring container 7 can be cleaned.

[0078] 2, the lower end 20a of the inlet pipe 20 is located below the lower surface 721 of the upper wall 72. The lower end 23a of the gas pipe 23 may be located below the lower surface 721 of the upper wall 72, but as shown in FIG. 2, the gas pipe 23 may be connected to the upper wall 72 at the same height as the lower surface 721 or above the lower surface 721.

[0079] If the cleaning liquid enters and remains in the gas piping 23, there is a possibility that it will mix with the liquid L that is subsequently supplied to the internal space 37. However, according to the configuration shown in Fig. 2, the cleaning liquid that has been supplied to the internal space 37 is less likely to enter the gas piping 23. Therefore, it is possible to prevent the cleaning liquid from mixing with the liquid L that is subsequently supplied.

[0080] The same applies to the discharge pipe 21. As shown in FIG. 2, the discharge pipe 21 may be connected to the upper wall 72 with the lower end 21a of the discharge pipe 21 positioned at the same height as the lower surface 721 of the upper wall 72 or higher than the lower surface 721.

[0081] [Regarding each type of measuring mechanism 15] As described above, the metering mechanism 15 of each of the above forms includes the metering container 7 having a closed internal space 37 in which liquid L is stored, the measuring instrument 26 for measuring the metering container 7, and the inlet pipe 20 that connects an upstream device such as the valve 14 to the metering container 7 and sends the liquid to the internal space 37. The inlet pipe 20 has an elastically deformable excess length portion 50.

[0082] Although the inlet pipe 20 is directly connected to the measuring container 7, the inlet pipe 20 has an excess length 50, so that even if tension is applied to the inlet pipe 20, the influence of the tension can be suppressed from affecting the measurement in the measuring container 7. As a result, the measuring mechanism 15 can accurately measure the liquid L.

[0083] In each of the above embodiments, the excess length 50 is located in the portion of the inlet pipe 20 that is connected to the upper wall 72 of the weighing container 7 in a hanging state. Therefore, even if tension acts on the portion of the inlet pipe 20 that is connected to the upper wall 72 of the weighing container 7 in a hanging state, it is possible to prevent the influence of that tension from affecting the weighing of the weighing container 7.

[0084] The measuring vessel 7 has a closed internal space 37. Therefore, in order to pressure-feed the liquid L in the measuring vessel 7 to the downstream reaction vessel 9, it is sufficient to supply gas to the measuring vessel 7. In other words, the outer vessel 93 as in the conventional system (see FIG. 5) is no longer necessary. This allows the measuring mechanism 15 and the synthesis apparatus 3 to be made smaller.

[0085] 〔others〕 In the case of the synthesis apparatus 3 shown in FIG. 4, the plurality of storage containers 2 are divided into two groups. The number of groups is not limited to this. For example, they may be grouped by treatment. In other words, when four treatments, namely, detritylation, coupling, oxidation, and capping, are performed, the storage containers 2 containing the liquid L used in each treatment may be included in one group. In other words, the plurality of storage containers 2 are divided into four groups.

[0086] In each of the above embodiments, the metering mechanism 15 has been described as being used in a synthesis device 3 for chemically synthesizing nucleic acids, but it may also be used in a synthesis device for chemically synthesizing proteins, peptides, etc.

[0087] The embodiments disclosed herein are illustrative in all respects and are not restrictive. The scope of the present invention is not limited to the above-described embodiments, but includes all modifications within the scope of the claims and equivalents thereof. [Explanation of symbols]

[0088] 2: Storage container 3: Synthesis device 7: Measuring container 7A: First measuring vessel 7B: Second measuring vessel 9: Reaction vessel 14: Valve (upstream equipment) 15: Metering mechanism 20: Inlet pipe 20A: First inlet pipe 20B: Second inlet pipe 21: Discharge pipe 22: downstream pipe 23: gas piping 24: liquid delivery means 25: Guide 26: Measuring instrument 26A: First measuring instrument 26B: Second measuring instrument 37: Internal space 50: Extra length 51: Yu Changbu 52: Yu Changbu 53: Yu Changbu 54: excess length 72: upper wall L: liquid C: Axis

Claims

1. a measuring container having a closed internal space and capable of storing a liquid; a measuring instrument for measuring the measuring container; an inlet pipe that is connected from an upstream device to the measuring container and sends liquid into the internal space; and The inlet pipe has an extra length that is elastically deformable. Metering mechanism.

2. The excess length portion is located at a portion of the inlet pipe that is connected to the upper wall of the measuring container in a hanging state. The metering mechanism of claim 1 .

3. The excess length portion has a linear shape along a spiral centered on an axis in the vertical direction.

3. A metering mechanism according to claim 1 or 2.

4. a plurality of said inlet pipes leading to said metered vessel; Among the plurality of inlet pipes, the excess length portion of a first inlet pipe and the excess length portion of a second inlet pipe located adjacent to the first inlet pipe are arranged at different heights. A weighing mechanism according to claim 1 or claim 2.

5. a guide for supporting a portion of the inlet pipe between the upstream device and the excess length portion; A weighing mechanism according to claim 1 or claim 2.

6. a discharge pipe connected to the measuring container for discharging gas from the internal space when the liquid is supplied to the measuring container through the inlet pipe; The discharge pipe has an excess length portion that is elastically deformable. A weighing mechanism according to claim 1 or claim 2.

7. a downstream pipe connected to the measuring container for sending liquid to a device downstream of the measuring container; a gas pipe for supplying gas to the interior space to pump the liquid in the measuring vessel through the downstream pipe; and The gas pipe has an elastically deformable excess length portion. A weighing mechanism according to claim 1 or claim 2.

8. A synthesis device for chemical synthesis by selectively sending a plurality of types of liquid, a liquid delivery means for delivering a plurality of types of liquid from a plurality of storage containers each containing the liquid; a measuring mechanism for measuring the liquid delivered by the liquid delivery means; a reaction vessel in which the liquid measured by the measuring mechanism is placed and a compound is produced; and The metering mechanism includes: a measuring container having a closed internal space and capable of storing the liquid; a measuring instrument for measuring the measuring container; an inlet pipe that is connected to an upstream device included in the liquid delivery means and that introduces liquid into the internal space of the measuring container; and The inlet pipe has an extra length that is elastically deformable. Synthesizer.

9. The metering mechanism includes: a first of the metered containers; a second of said metered vessels; a first measuring instrument for measuring a first measuring vessel; a second measuring instrument for measuring a second measuring vessel; and a first inlet pipe that is connected from the upstream device to the first measuring container and introduces liquid into the internal space; a second inlet pipe that is connected from the upstream device to the second measuring container and introduces liquid into the internal space; and the first inlet pipe has the excess length portion that is elastically deformable, The second inlet pipe has the excess length portion that is elastically deformable. The synthesis apparatus according to claim 8 .

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