Reaction device and measuring device

Abstract

This reaction device, which reduces the possibility of aerosols derived from discarded waste liquid being mixed into unused reagents, comprises a reaction chamber in which a reaction is carried out to fix a reaction product to a translucent array plate using a plate unit which comprises the array plate and an embankment portion and in which a liquid can be collected, a chemical liquid placement portion which is disposed within the reaction chamber and on which a container for storing a liquid specimen or a chemical liquid to be supplied to the array plate is placed, a liquid discarding portion which is disposed within the reaction chamber and into which the liquid that has been collected in the array plate after the liquid specimen or the chemical liquid has been supplied is discarded, and a reaction chamber evacuating portion which evacuates the atmosphere within the reaction chamber to reduce the pressure, wherein the liquid discarding portion is positioned closer to the reaction chamber evacuating portion than the chemical liquid placement portion.

Description

Reactor and measuring device

[0001] The present disclosure relates to a reactor, particularly to a reactor having a reaction chamber for carrying out a reaction in which a reaction product is immobilized on an array plate, and to a measurement device.

[0002] Array plates such as protein arrays, peptide arrays, and DNA arrays are known, in which a large number of substances such as proteins, peptides, and nucleic acids are fixed in the form of spots on a substrate. By using such array plates, interactions between a large number of fixed substances and substances in a specimen can be observed simultaneously. This allows comprehensive analysis of interactions between a liquid specimen derived from a living body, such as blood, cell extract, saliva, or interstitial fluid, and a large number of substances, such as a drug solution.

[0003] A known measurement method using an array plate involves selectively fluorescently labeling spots where an interaction of interest has occurred to obtain optical information. A known device for observing fluorescently labeled specimens is a confocal laser microscope. The confocal laser microscope comprises an illumination optical system, a fluorescence detection optical system, and a two-dimensional scanning system. The fluorescence detection optical system has the function of detecting the amount of fluorescence from spots labeled with fluorescent probes. The two-dimensional scanning system has the function of acquiring a fluorescent image of the spot area on the array plate by two-dimensionally scanning the array plate or the optical system.

[0004] Patent Document 1 discloses a specimen evaluation device. In this specimen evaluation device, a frame capable of storing liquid is fixed to an array plate, and a pipette tip is moved above the array plate to sequentially supply and discharge multiple chemical solutions to cause reactions. After these reaction steps are completed, the liquid-retaining state is maintained and optical scanning measurement is performed to obtain a fluorescent image of the spot area.

[0005] The proteins, etc., immobilized on the array plate are subjected to a dispensing process to supply a liquid specimen or a chemical solution, or a drainage process to drain the liquid from the proteins, etc., after the reaction. These supply and drainage processes are carried out in a reaction device having a reaction chamber provided as a substantially closed space. Measurements using the array plate are carried out in a measurement device arranged to communicate with the reaction device, such as the sample measurement device exemplified in Patent Document 1, and such a reaction device, together with the measurement device, constitutes a sample evaluation device.

[0006] Japanese Patent Application Laid-Open No. 2023-012426

[0007] In the sample evaluation device including a reaction chamber described in Patent Document 1, liquid replacement, such as dispensing and draining, is performed during the process of obtaining a reaction product. The liquid (waste liquid) discharged from the array plate during liquid replacement is disposed of in a designated area for hygiene and safety reasons. The atmosphere in the reaction chamber may become a mixed phase (separated phase) containing aerosols derived from the waste liquid due to the state in which the waste liquid stored in the waste area comes into contact with the atmosphere inside the reaction chamber, or due to the bursting of air bubbles in the liquid at the tip of a pipette tip or the falling of droplets when the waste liquid is disposed of in the waste area. Such aerosols may reach the storage area for reagents scheduled for use in the reaction process due to convection in the atmosphere inside the reaction chamber, potentially contaminating unused reagents. Furthermore, since the waste liquid discharged from the array plate and stored in the waste area contains multiple used specimens and post-reaction chemicals, there is a concern that if some of the aerosols derived from the waste liquid are mixed with other specimens or chemicals, it may affect the measurement results.

[0008] Furthermore, in the above-described measuring device, if a portion of the aerosol likely to contain an antibody component containing a labeling substance reaches the measurement chamber from the reaction chamber, the aerosol increases the background light contained in the secondary light, which may affect the measurement results.

[0009] The present disclosure has been made in consideration of such circumstances, and aims to provide a reaction device having a reaction chamber that reduces the possibility of aerosol components derived from discarded waste liquid being mixed into unused reagents.

[0010] In order to solve the above problems, a reaction apparatus according to one aspect of the present disclosure comprises: a reaction chamber in which a reaction is carried out to fix a reaction product to the array plate using a plate unit having a translucent array plate and a bank portion and capable of storing a liquid; a chemical liquid mounting portion disposed within the reaction chamber and on which a container for storing a liquid specimen or chemical liquid to be supplied to the array plate is mounted; a liquid disposal portion disposed within the reaction chamber and which discards the liquid stored in the array plate after the liquid specimen or chemical liquid has been supplied; and a reaction chamber exhaust portion which evacuates and reduces the pressure of the atmosphere within the reaction chamber, wherein the liquid disposal portion is located closer to the reaction chamber exhaust portion than the chemical liquid mounting portion.

[0011] According to one aspect of the present disclosure, a reaction device having a reaction chamber that reduces the possibility of aerosol components derived from discarded waste liquid being mixed into unused reagents can be provided.

[0012] Fig. 1 is a schematic cross-sectional view from above showing an example of the internal structure of a reaction device according to a first embodiment of the present disclosure. Fig. 2 is a schematic front view showing the internal structure of the reaction device exemplified in Fig. 1. Fig. 3 is a schematic cross-sectional view from the right side showing the internal structure of the reaction device exemplified in Fig. 1. Fig. 4 is a schematic cross-sectional view from above showing an example of the internal structure of a measurement device according to a second embodiment of the present disclosure. Fig. 5 is a schematic cross-sectional view from the right side showing the internal structure of the measurement device exemplified in Fig. 4.

[0013] Exemplary embodiments for implementing the present disclosure will be described in detail below with reference to the accompanying drawings. Note that the following embodiments do not limit the invention according to the claims. Although multiple features are described in the embodiments, not all of these multiple features are necessarily essential to the invention, and multiple features may be combined arbitrarily. Furthermore, the dimensions, materials, shapes, and relative positions of components described in the following embodiments are arbitrary and can be changed depending on the configuration of the device to which the present disclosure is applied or various conditions. Furthermore, in the accompanying drawings, the same reference numbers will be used between drawings to indicate identical or functionally similar elements, and redundant explanations will be omitted.

[0014] (First embodiment) Hereinafter, an example of a reaction apparatus according to a first embodiment of the present disclosure will be described with reference to Figs. 1 to 3. Figs. 1, 2, and 3 are cross-sectional views each showing a schematic view of the internal structure of an example of a reaction apparatus according to the first embodiment, as viewed from above, from the front, and from the right, respectively. The view taken along the arrow 1A-1A' in Fig. 2 corresponds to Fig. 1. Similarly, the view taken along the arrow 1B-1B' in Fig. 2 corresponds to Fig. 3.

[0015] The reaction device 100 according to this embodiment is capable of carrying out a reaction process on a plurality of array plates 1. In the reaction process, a liquid specimen derived from a living organism and a chemical solution are sequentially reacted with a large number of spot-like proteins fixed on the upper surface of the array plate 1, and then fluorescent labeling is performed. For this purpose, a frame member 2 that forms a bank for storing the chemical solution and the like is attached to the array plate 1, and these together form a plate unit 3. The reaction device 100 is configured so that the reaction process can be carried out on a plurality of plate units 3 housed in a reaction chamber 4.

[0016] The illustrated reaction apparatus 100 includes a reaction chamber 4, an array plate mounting unit, a dispenser unit, a chemical supply and discharge unit, and an exhaust unit. Each unit will be described below. The array plate mounting unit, the dispenser unit, and the chemical supply and discharge unit are provided in the reaction chamber 4, and the exhaust unit can exhaust the inside of the reaction chamber 4 and reduce the pressure inside the reaction chamber 4.

[0017] In the reaction apparatus 100, the array plate mounting unit includes, for example, an array plate mounting section 5, a shaking table 6, and a unit table 7. The plate unit 3 described above is mounted on the upper surface of the array plate mounting section 5. The array plate mounting section 5 can regulate the position of the plate unit 3, for example, by fitting pins. The array plate mounting section 5 is also provided with a temperature control block, which is configured to be in thermal contact with the underside of the array plate 1. The array plate mounting section 5 is also fixed to a shaking table 6 equipped with a reciprocating mechanism (not shown) that can shake the array plate 1 in the Y-axis direction. FIG. 1 illustrates a state in which five array plate mounting sections 5 and shaking tables 6 are arranged on the unit table 7 inside the reaction chamber 4, and plate units 3 are installed on each of the four array plate mounting sections 5 on the left side.

[0018] The temperature control block in the array plate mounting section 5 is capable of independently heating and temperature control for each plate unit 3. The shaking table 6 is also capable of independently shaking each plate unit 3. By combining these operations and maintaining a predetermined constant temperature through heating and temperature control while performing shaking, it is possible to promote the reaction between the array plate 1 and the stored chemical solution and maintain reaction uniformity across multiple spots within the array plate 1. Furthermore, the array plate mounting unit according to this embodiment is configured so that operational instructions regarding temperature and shaking can be set independently for each array plate 1 using a controller (not shown).

[0019] The dispenser unit is configured to move a dispenser 18, to which disposable pipette tips 17 can be attached, between various parts of the chemical solution supply and discharge unit described below, and to supply or discharge chemical solutions to or from the plate unit 3. The dispenser unit has the dispenser 18 including a pipetter, and a dispensing actuator that moves the dispenser 18. The dispensing actuator is made up of an X-axis dispensing actuator 19, a Y-axis dispensing actuator 20, and a Z-axis dispensing actuator 21, and allows the dispenser 18 to move in three axial directions.

[0020] In this embodiment, the chemical liquid supply and discharge unit includes a tip mounting section 9, a chemical liquid mounting section 13, a tip disposal section 12, and a liquid disposal section 8 provided within the reaction chamber 4. The tip mounting section 9 is provided for storing a plurality of pipette tips, and in this embodiment, includes a liquid supply tip mounting section 10 for storing pipette tips used when supplying chemical liquids, etc., and a liquid discharge tip mounting section 11 for storing pipette tips used when discharging. The chemical liquid mounting section 13 stores a plurality of liquid specimens and chemical liquids. The tip disposal section 12 is provided for storing used pipette tips that are pipette tips used to supply liquid specimens and chemical liquids, and used pipette tips that are pipette tips used to discharge waste liquids. The liquid disposal section 8 is provided for storing waste liquids consisting of used specimens and chemical liquids discharged from proteins, etc. after a reaction. The waste liquid mentioned here is a general term for liquid that is present in an array plate to which a liquid specimen or chemical solution has been supplied, for example, prior to measurement, and that should be removed during measurement.

[0021] The sequence of operations for supplying a chemical solution to the plate unit 3 using the dispensing unit and the chemical solution supply and discharge unit is as follows. First, the dispenser 18 is moved to the liquid supply tip mounting section 10 by three actuators in the dispensing unit, and the pipette tip 17 held in the liquid supply tip mounting section 10 is attached to the tip of the dispenser 18. Next, the dispenser 18 with the pipette tip 17 attached is moved to the chemical solution mounting section 13. The chemical solution mounting section 13 holds various liquid specimens and chemical solutions used in the reaction process. The dispenser 18 then aspirates the liquid specimen or chemical solution required for the reaction process. Thereafter, the dispenser 18 is moved above the plate unit 3 while aspirating and holding the chemical solution, and dispensing is performed to supply the aspirated and held chemical solution to a predetermined spot on the array plate 1 on the plate unit 3. After dispensing, the dispenser 18 is moved to the tip disposal unit 12 , and the used pipette tip 17 is detached from the dispenser 18 and disposed of in the tip disposal unit 12 .

[0022] After the reaction, the chemical solution or the like present in the spot is discharged. To discharge the chemical solution or the like, first, the dispenser 18 is moved to the discharge tip mounting portion 11, and the pipette tip 17 held in the discharge tip mounting portion 11 is attached to the tip of the dispenser 18. Next, the dispenser 18 with the pipette tip 17 attached is moved to the plate unit 3, where the chemical solution or the like is discharged. The dispenser 18 aspirates the chemical solution or the like from a predetermined spot on the array plate 1 on the plate unit 3. Then, while holding the aspirated chemical solution or the like, the dispenser 18 is moved to the liquid disposal portion 8, and any unnecessary chemical solution or the like in the pipette tip 17 is discharged to the liquid disposal portion 8 as waste liquid. After discharging the chemical solution or the like, the dispenser 18 is further moved to the tip disposal portion 12, and the used pipette tip 17 is detached from the dispenser 18 and disposed of in the tip disposal portion 12.

[0023] In the present disclosure, the reaction chamber 4 is isolated from the outside air by the reaction chamber housing 23. The inside of the reaction chamber 4 is depressurized by an exhaust unit described below. The exhaust unit in this embodiment has, for example, a reaction chamber exhaust section 14, a reaction chamber exhaust port 15, and a reaction chamber intake section 16. The reaction chamber exhaust port 15 and the opening that constitutes the reaction chamber intake section 16 are provided in the reaction chamber housing 23, and constitute a gas outlet and inlet for the reaction chamber housing 23.

[0024] The reaction chamber intake section 16 has the opening described above for taking in air from the outside into the reaction chamber 4, and a dust filter attached to the opening to prevent dust and the like from entering the reaction chamber 4. The reaction chamber exhaust port 15 is an opening provided in the reaction chamber housing 23, and the inside of the reaction chamber 4 is connected to the reaction chamber exhaust section 14 via the reaction chamber exhaust port 15. The reaction chamber exhaust section 14 is equipped with an exhaust fan 38 and a particle absorption filter 37 such as a HEPA (high-efficiency particulate air) filter. By reducing the pressure inside the reaction chamber 4 using the exhaust fan 38, outside air is introduced into the reaction chamber 4 through the reaction chamber intake section 16, and the atmosphere inside the reaction chamber 4 is released to the outside via the particle absorption filter 37 of the reaction chamber exhaust section 14.

[0025] When aerosols floating within the reaction chamber 4 are generated due to evaporation during dispensing or waste liquid discharge within the reaction chamber 4, these aerosols are adsorbed by the particle adsorption filter 37 by discharging the gas within the reaction chamber 4 to the outside through the particle adsorption filter 37. In this specification, "evaporation" includes droplets that bounce off the liquid phase as droplets fall from the pipette tip (microdroplets due to liquid splashing), microdroplets generated by the bursting of bubbles in the liquid phase, and the scattering of satellite liquid. By discharging the gas within the reaction chamber 4 to the outside through the particle adsorption filter 37, leakage of aerosols outside the device can be prevented. For example, HEPA filters are known to be effective in removing viruses. When handling particularly infectious samples, adsorbing the aerosols described above to this HEPA filter can prevent the virus from being released outside the device.

[0026] When multiple array plates are used in the reaction chamber 4, as in this embodiment, there is a concern that aerosols generated in one array plate may contaminate other array plates and affect the reaction state. Because the liquid waste unit 8 stores used chemical solutions containing multiple specimens as waste liquid, the impact of aerosols generated therefrom must be more strictly reduced. In this embodiment, the liquid waste unit 8, which stores the waste liquid, is positioned closer to the reaction chamber exhaust port 15 than any of the multiple array plates 1. While it is difficult to identify a specific flow due to the various configurations provided within the reaction chamber 4, the reaction chamber exhaust unit 14 generates an airflow within the reaction chamber 4 that generally flows from the reaction chamber intake unit 16 toward the reaction chamber exhaust port 15. By positioning the array plate 1 farther from the liquid waste unit 8 than the reaction chamber exhaust port 15 and approximately upstream of the airflow, the possibility of aerosols resulting from the waste liquid stored in the liquid waste unit 8 adhering to or contaminating the array plate 1 can be reduced.

[0027] Furthermore, in this embodiment, the liquid disposal unit 8 can be located closer to the reaction chamber exhaust unit 14 than the chemical liquid mounting unit 13. That is, in this embodiment, the liquid disposal unit 8 can be located substantially downstream of the above-described airflow in the reaction chamber 4 relative to other components of the chemical liquid supply and discharge unit, such as the chemical liquid mounting unit 13. By locating the liquid disposal unit 8 in this manner, it is possible to reduce the possibility that aerosols originating from the liquid (waste liquid) stored in the liquid disposal unit 8 will adhere to or be mixed into the pre-reaction liquid specimen or chemical liquid in the chemical liquid mounting unit 13, for example.

[0028] Furthermore, in this embodiment, the liquid disposal unit 8 is disposed closer to the reaction chamber exhaust unit 14 than the tip disposal unit 12. Aerosols resulting from waste liquid may be generated due to used pipette tips. However, it can be assumed that the likelihood of aerosol generation due to waste liquid adhering to pipette tips present in the tip disposal unit 12 is lower than the likelihood of aerosol generation due to waste liquid in the liquid disposal unit 8. Therefore, in this embodiment, the positional relationship between the liquid disposal unit 8 and the tip disposal unit 12 is defined as described above.

[0029] Furthermore, in this embodiment, the tip mounting section 9 is divided into a liquid supply tip mounting section 10 and a liquid discharge tip mounting section 11. However, the liquid discharge tip mounting section 11 may be integrated on the liquid supply tip mounting section 10 side, with the chemical solution mounting section 13 positioned closer to the reaction chamber exhaust port 15 than the liquid supply tip mounting section 10. When the tip mounting section is divided into two sections as in this embodiment, it is preferable to position the liquid supply tip mounting section 10 so as to reduce the possibility of aerosols adhering to pipette tips used for pre-reaction liquid samples, chemical solutions, etc. Therefore, in this embodiment, the liquid discharge tip mounting section 11 is positioned closer to the reaction chamber exhaust port 15 than the liquid supply tip mounting section 10. Furthermore, it is desirable to further reduce the possibility of aerosols adhering to pipette tips used during dispensing. Therefore, in this embodiment, the liquid supply tip mounting section 10 is positioned farther from the liquid disposal section 8 and the tip disposal section 12 than the liquid discharge tip mounting section 11. Furthermore, with regard to the airflow described above, the liquid supply tip mounting part 10 is disposed substantially upstream of the liquid discharge tip mounting part 11 .

[0030] Furthermore, in this embodiment, an example has been shown in which a single dispenser 18 is used within the device to supply and discharge a medicinal liquid, etc., but two dispensers, one for supply and one for discharge, may be used. In this case, a separate dispensing actuator is required, but some actuators may be shared. Furthermore, in such a configuration, actuators other than the Cartesian coordinate system-controlled dispensing actuator that moves in the X, Y, and Z axes described above may be used. Specifically, for example, the dispensing actuator for drainage may be a polar coordinate system-controlled dispensing actuator (RθZ position control) that combines an actuator that rotates around the Y axis with the Z axis. Using a polar coordinate system-controlled dispensing actuator eliminates the need for the dispenser 18 that discharges the liquid to move to the medicinal liquid placement unit 13, which is expected to reduce the possibility of aerosols reaching and contaminating the medicinal liquid placement unit 13.

[0031] As described above, the reaction device 100 according to one embodiment of the present disclosure includes a reaction chamber 4, a chemical liquid placement unit 13, a liquid disposal unit 8, and a reaction chamber exhaust unit 14. The reaction chamber 4 includes a light-transmitting array plate 1 and a bank (frame member 2), and is used to carry out a reaction in a plate unit 3 capable of storing a liquid, in which a reaction product is fixed to the array plate 1. The chemical liquid placement unit 13 is disposed within the reaction chamber 4, and a container for storing a liquid specimen or a chemical liquid to be supplied to the array plate 1 is placed thereon. The liquid disposal unit 8 is disposed within the reaction chamber, and is used to discard the liquid stored in the array plate 1 after the liquid specimen or the chemical liquid has been supplied. The reaction chamber exhaust unit 14 is used to reduce the pressure inside the reaction chamber. In the reaction device 100 according to one embodiment of the present disclosure having the above configuration, the liquid disposal unit 8 is located closer to the reaction chamber exhaust unit 14 than the chemical liquid placement unit 13.

[0032] The reaction device 100 may also include, within the reaction chamber 4, a tip mounting section 9 on which a pipette tip 17 is mounted, and a tip disposal section 12. The pipette tip 17 is attached to the tip of the dispenser 18 and used when a liquid specimen or a chemical solution stored in the above-mentioned container is supplied to the array plate 1 using the dispenser 18. The pipette tip 17 is attached to the tip of the dispenser 18 and used when a liquid stored in the array plate 1 after supplying the liquid specimen or chemical solution is discharged using the dispenser 18. The pipette tip 17 attached to the dispenser 18 is mounted on the tip mounting section 9. The tip disposal section 12 is used to discard used pipette tips that have been removed from the dispenser 18.

[0033] In the reaction apparatus 100 described above, the liquid disposal unit 8 can be located closer to the reaction chamber exhaust unit 14 than the tip disposal unit 12. The tip mounting unit 9 can include a liquid supply tip mounting unit 10 and a liquid discharge tip mounting unit 11. A pipette tip 17 is mounted on the liquid supply tip mounting unit 10 and used to supply a liquid specimen or a liquid drug stored in a container to the array plate 1. The liquid discharge tip mounting unit 11 is mounted on a pipette tip used to drain liquid stored in the array plate 1 after supplying the liquid specimen or liquid drug. The liquid discharge tip mounting unit 11 can be located closer to the reaction chamber exhaust unit 14 than the liquid supply tip mounting unit 10. The reaction chamber exhaust unit 14 can include an exhaust fan 38 as a means for reducing the pressure in the reaction chamber 4. In addition to the exhaust fan 38, the reaction chamber exhaust unit 14 can include a particle adsorption filter 37 that is located upstream of the exhaust fan 38 and is capable of adsorbing aerosols contained in the gas within the reaction chamber 4. In this case, the particle adsorption filter 37 may include a HEPA filter.

[0034] According to one aspect of the reaction device 100 of the present disclosure, a liquid disposal unit 8 that discards the liquid stored in the array plate 1 and a chemical liquid mounting unit 13 that stores the liquid specimen or chemical liquid to be supplied to the array plate 1 are arranged in order of proximity to the reaction chamber exhaust unit 14 that depressurizes the reaction chamber 4. As a result, even if aerosols are generated in the liquid disposal unit 8, they are sucked into the reaction chamber exhaust unit 14 located nearby, reducing the possibility that aerosols floating within the reaction device 100 will adhere to components in the reaction chamber, the array plate 1 before reaction, the liquid specimen or chemical liquid, etc.

[0035] Second Embodiment Next, a measurement device according to a second embodiment of the present disclosure will be described with reference to Figures 4 and 5. Figures 4 and 5 are cross-sectional views schematically showing the internal structure of the measurement device according to this embodiment, as viewed from above and from the right, respectively. Note that components having the same functions as those described in the first embodiment above will be denoted by the same reference numerals, and detailed description thereof will be omitted below.

[0036] The measuring device 200 according to this embodiment is configured such that a measurement chamber 24 is provided in addition to the reaction chamber 4 described in the first embodiment. In the measuring device 200, the array plate 1 that has completed the reaction process in the reaction chamber 4 is moved to the measurement chamber 24 side, and optical measurement is performed in the measurement chamber 24.

[0037] The measurement chamber 24 includes a measurement chamber plate unit transport unit and a measurement unit, which are arranged inside the measurement chamber housing 30. The measurement chamber plate unit transport unit has a plate transport hand 25, a transport Y-axis stage 27, and a transport Z-axis stage 26. The plate transport hand 25 is capable of placing a plate unit 3 having an array plate 1 thereon, and transports the plate unit 3 into and out of the reaction chamber 4. The transport Z-axis stage 26 drivably supports the plate transport hand 25 and moves the plate transport hand 25 in the Z-axis direction. The transport Y-axis stage 27 drivably supports the transport Z-axis stage 26 and moves the plate transport hand 25 in the Y-axis direction together with the transport Z-axis stage 26.

[0038] In this embodiment, a moving table 22 is provided below the unit table 7 in the reaction chamber 4, allowing the unit table 7 to move in the X-axis direction. During measurement, the moving table 22 allows the plate transport hand 25 to move into the reaction chamber 4, allowing the plate unit 3 in the reaction chamber 4 to be moved in the X-axis direction to a position where the plate unit 3 can be transferred.

[0039] The measurement unit has an optical detection system 29 and an optical scanning system 28. The optical detection system 29 generates laser light having a specific wavelength that is irradiated onto the array plate 1 as primary light, and detects fluorescence, which is secondary light emitted by the irradiation of the primary light. The optical scanning system 28 is provided so that the irradiation position of the primary light can be moved back and forth in the X-axis direction so that the primary light can be irradiated onto a large number of proteins on the array plate 1.

[0040] As described above, measurement of spot-like proteins on the array plate 1 is performed while the plate unit 3 delivered by the plate transport hand 25 is placed on the plate transport hand 25. Specifically, laser light having a specific wavelength generated by the optical detection system 29 is irradiated as primary light onto the array plate 1 via the optical scanning system 28. When this primary light is irradiated onto spot-like proteins that have been fluorescently labeled in the reaction process, fluorescent light is emitted from the proteins as secondary light. The secondary light travels in the opposite direction along the optical path of the irradiated primary light and is detected by the optical detection system 29. The optical scanning system 28 is capable of reciprocating movement in the X-axis direction to measure the numerous proteins on the array plate 1, and in combination with Y-axis movement by the transport Y-axis stage 27, enables two-dimensional X- and Y-dimensional measurement within the plane of the array plate.

[0041] The measurement chamber 24 and the reaction chamber 4 are surrounded by a measurement chamber housing 30 and a reaction chamber housing 23, respectively, and a partition wall 32 is provided between the two chambers to separate them. In this embodiment, the partition wall 32 constitutes a part of the reaction chamber housing 23 and also a part of the measurement chamber housing 30. In other words, the reaction chamber housing 23 and the measurement chamber housing 30 are integrally connected via the partition wall 32. An open inter-chamber communication port 33 is provided in the partition wall 32. The plate transport hand 25 carries the plate unit 3 out of the reaction chamber 4 through the inter-chamber communication port 33 and into the measurement chamber.

[0042] Furthermore, the measurement chamber housing 30 is provided with a measurement chamber intake section 31 having an opening for allowing outside air to flow into the measurement chamber 24 and a dust filter. By operating the exhaust fan 38 of the reaction chamber exhaust section 14, air flowing into the measurement chamber 24 from the measurement chamber intake section 31 passes through the inter-chamber communication port 33 and flows into the reaction chamber 4. The air flowing into the measurement chamber 24 from the measurement chamber intake section 31, together with air flowing into the reaction chamber 4 from the reaction chamber intake section 16, is then discharged to the outside of the measurement device 200 through the particle adsorption filter 37 from the reaction chamber exhaust port 15. At this time, in this embodiment, the pressure inside the reaction chamber 4 is reduced relative to the atmospheric pressure outside the measurement device 200. As a result, the air inside the reaction chamber 4 does not leak to the outside except through the particle adsorption filter 37, and aerosols generated in the reaction chamber 4 are adsorbed by the particle adsorption filter 37, preventing the aerosols from leaking outside the measurement device 200.

[0043] For this reason, in this embodiment, the reaction chamber intake section 16 and the measurement chamber intake section 31 are each designed to have a higher intake resistance than the reaction chamber exhaust port 15. This makes it easy to reduce the pressure inside the reaction chamber 4 and the measurement chamber 24. Furthermore, it is desirable to make the reaction chamber intake section 16 have a higher intake resistance than the measurement chamber intake section 31, so that the pressure inside the reaction chamber 4 is negative relative to the pressure inside the measurement chamber 24. This configuration prevents air from flowing from the reaction chamber 4 into the measurement chamber 24, and reduces the possibility of aerosols adhering to the optical detection system 29.

[0044] Furthermore, the reaction chamber housing 23 is provided with an access port 34 used for inserting and removing the plate unit 3, and a port closing section 35 having a mechanism for opening and closing the access port 34. The access port 34 and the port closing section 35 are configured so that the access port 34 is airtightly closed via a conductive and elastic sealing member 39. As a result, the inflow of outside air into the reaction chamber 4 is limited to that via the reaction chamber intake section 16 and the measurement chamber intake section 31 via the inter-chamber communication port 33. The reaction chamber housing 23 is also electrically connected to a grounding point outside the measurement device via a grounding member 36 made of a cable or the like. As a result, the entire housing of the measurement device 200, including the measurement chamber housing 30, is grounded, thereby reducing the effects of electromagnetic waves and the like.

[0045] As described above, the measurement device 200 according to one aspect of the present disclosure includes a reaction chamber 4, a measurement chamber 24, a liquid disposal unit 8, and a reaction chamber exhaust unit 14. The reaction chamber 4 includes a light-transmitting array plate 1 and a bank (frame member 2), and is used to carry out a reaction to immobilize a reaction product in a plate unit 3 capable of storing a liquid. The measurement chamber 24 is connected to the reaction chamber 4 via an inter-chamber communication port 33 and is used to optically measure the distribution of the reaction product on the array plate 1 transferred from the reaction chamber 4. The reaction chamber exhaust unit 14 is used to reduce the pressure inside the reaction chamber and the measurement chamber. This configuration reduces the possibility of aerosols formed in the reaction chamber 4 propagating into the measurement chamber 24 due to the reduced pressure inside the reaction chamber.

[0046] The above-described measuring device 200 further includes a reaction chamber intake unit 16 in the reaction chamber 4, which is used to introduce outside air into the reaction chamber. The reaction chamber intake unit 16 can be set to have a higher intake resistance than the reaction chamber exhaust port 15, which is provided in the reaction chamber 4 and connects the reaction chamber to the reaction chamber exhaust unit 14. The measuring device 200 can also include a measurement chamber intake unit 31 in the measurement chamber 24, which has a higher intake resistance than the reaction chamber exhaust port 15 and is provided to introduce outside air into the measurement chamber 24. The intake resistance of the reaction chamber intake unit 16 can be set to be higher than the intake resistance of the measurement chamber intake unit 31. In the measuring device 200 according to one aspect of the present disclosure having the above configuration, the reaction chamber exhaust unit 14 generates an airflow in the reaction chamber 4 toward the reaction chamber exhaust unit 14, and the air in the reaction chamber is exhausted to the outside via the reaction chamber exhaust unit 14. An airflow is also generated in the measurement chamber 24 toward the reaction chamber 4 via the inter-chamber communication port 33. In such a configuration, for example, by locating the liquid disposal unit 8 closer to the reaction chamber exhaust unit 14 than the position where the inter-chamber communication port is provided, aerosols resulting from the liquid disposal unit 8 or the disposal of liquid into the liquid disposal unit 8 are quickly discharged from inside the reaction chamber 4 to the outside via the reaction chamber exhaust unit 14. Therefore, the propagation of aerosols to areas other than the area where the liquid disposal unit 8 is located within the reaction chamber 4 is suppressed, and further, the possibility of aerosols propagating to the measurement chamber 24 against the airflow formed at the chamber-to-chamber communication port can be reduced.

[0047] The above-described measuring device 200 further includes a reaction chamber housing 23 that constitutes the reaction chamber 4, and a measurement chamber housing 30 that constitutes the measurement chamber 24. In this case, the reaction chamber housing 23 and the measurement chamber housing 30 can share a partition wall in which an inter-chamber communication port 33 that connects the reaction chamber 4 and the measurement chamber 24 is provided. The measurement chamber 24 in the measuring device 200 can further be provided with an optical scanning system 28 that scans the array plate 1 with primary light, and an optical detection system 29 that detects secondary light emitted from the array plate 1 in response to irradiation with the primary light.

[0048] In the above-described measuring device 200, the reaction chamber housing 23 constituting the reaction chamber 4 and the measurement chamber housing 30 constituting the measurement chamber 24 are both conductive and can be commonly grounded via a grounding member 36. The measuring device 200 can further include an access port 34 for inserting and removing the plate unit 3 into and from the reaction chamber, and a port closing unit 35 for opening and closing the access port 34. In this case, the port closing unit 35 can be grounded via the reaction chamber housing 23 constituting the reaction chamber 4 and in which the access port 34 is provided. The access port 34 can be closed by the port closing unit 35 via a conductive and elastic seal member 39. A seal member (not shown) is disposed on at least one of the access port 34 and the port closing unit 35. The seal member's elasticity, which extends continuously in the circumferential direction, ensures an annular sealing function. The seal member has continuous conductivity in the thickness direction (opening / closing direction) of the seal member.

[0049] The measuring device 200 described above also has a chemical liquid placing unit 13 and a liquid disposal unit 8. As described above, the chemical liquid placing unit 13 is disposed within the reaction chamber 4, and a container for storing a liquid specimen or chemical liquid to be supplied to the array plate 1 is placed thereon. The liquid disposal unit 8 is disposed within the reaction chamber 4, and is used to discard the liquid stored in the array plate after the liquid specimen or chemical liquid has been supplied. In this embodiment, too, the liquid disposal unit 8 can be positioned closer to the reaction chamber exhaust unit 14 than the chemical liquid placing unit 13. The reaction chamber 4 also has a tip placing unit 9 on which an unused pipette tip 17 is placed, and a tip disposal unit 12 on which pipette tips 17 removed from the dispenser 18 are discarded. Since the removed pipette tip 17 has waste liquid that has been discarded in the liquid disposal section 8 attached to it, the tip disposal section 12 can also be positioned near the reaction chamber exhaust section 14 and adjacent to the liquid disposal section 8 so as to achieve the same effect as the positioning of the liquid disposal section 8.

[0050] With the above-described configuration, the measuring device according to one aspect of the present disclosure can reduce the possibility of aerosols caused by waste liquid generated in or near the liquid waste unit 8 propagating into the measurement chamber 24. This reduces the possibility of aerosols adhering to unexpected locations, and reduces the possibility of errors in the measurement results caused by aerosols for proteins or the like supplied with a liquid specimen or a medicinal liquid.

[0051] The present invention is not limited to the above-described embodiments, and various modifications and variations can be made without departing from the spirit and scope of the present invention. Therefore, the following claims are appended to apprise the public of the scope of the present invention.

[0052] This application claims priority based on Japanese Patent Application No. 2024-019687, filed February 13, 2024, the entire contents of which are incorporated herein by reference.

[0053] 1: Array plate 2: Bank portion 3: Plate unit 4: Reaction chamber 5: Array plate mounting portion 6: Shaking table 7: Unit table 8: Liquid disposal portion 9: Tip mounting portion 10: Liquid supply tip mounting portion 11: Liquid discharge tip mounting portion 12: Tip disposal portion 13: Chemical liquid mounting portion 14: Reaction chamber exhaust portion 15: Reaction chamber exhaust port 16: Reaction chamber intake portion 17: Pipette tip 18: Dispenser 19: X-axis dispensing actuator 20: Y-axis dispensing actuator 21: Z-axis dispensing actuator 22: Moving table 23: Reaction chamber housing 24: Measurement chamber 25: Plate transport hand 26: Z-axis transport stage 27: Y-axis transport stage 28: Optical scanning system 29: Optical detection system 30: Measurement chamber housing 31: Measurement chamber intake portion 32: Partition portion 33: Inter-chamber communication port 34: Access port 35: Port closure 36: Grounding member 37: Particle adsorption filter 38: Exhaust fan 39: Seal member 100: Reactor 200: Measuring device

Claims

1. A reaction apparatus comprising: a reaction chamber in which a reaction is carried out to fix a reaction product to the array plate using a plate unit having a translucent array plate and a bank portion and capable of storing a liquid; a chemical liquid mounting portion located within the reaction chamber and on which a container for storing a liquid specimen or chemical liquid to be supplied to the array plate is mounted; a liquid disposal portion located within the reaction chamber and for discarding the liquid stored in the array plate after the liquid specimen or chemical liquid has been supplied; and a reaction chamber exhaust portion for evacuating and reducing the pressure of the atmosphere within the reaction chamber, wherein the liquid disposal portion is located closer to the reaction chamber exhaust portion than the chemical liquid mounting portion.

2. The reaction apparatus according to claim 1, further comprising: a tip mounting section for mounting a pipette tip attached to a dispenser used when supplying the liquid specimen or chemical solution stored in the container to the array plate or when discharging the liquid stored in the array plate after supplying the liquid specimen or chemical solution; and a tip disposal section for disposing of the pipette tip removed from the dispenser.

3. The reaction device according to claim 2, wherein the liquid disposal section is located closer to the reaction chamber exhaust section than the tip disposal section.

4. A reaction apparatus as described in claim 2 or 3, wherein the tip mounting section has a liquid supply tip mounting section on which a pipette tip used to supply the liquid specimen or chemical solution stored in the container to the array plate is mounted, and a liquid discharge tip mounting section on which a pipette tip used to discharge the liquid stored in the array plate after the liquid specimen or chemical solution has been supplied is mounted.

5. The reaction device according to claim 4, wherein the discharge tip mounting portion is located closer to the reaction chamber exhaust portion than the liquid supply tip mounting portion.

6. The reactor according to any one of claims 1 to 5, wherein the reaction chamber exhaust comprises an exhaust fan and a particle adsorption filter.

7. The reactor of claim 6, wherein the particulate adsorption filter comprises a HEPA filter.

8. A measuring device comprising: a reaction chamber in which a reaction is carried out to fix a reaction product to the array plate using a plate unit having a light-transmitting array plate and a bank portion and capable of storing a liquid; a measurement chamber that is connected to the reaction chamber via an inter-chamber communication port and optically measures the distribution of the reaction product on the array plate transported from the reaction chamber; and a reaction chamber exhaust section that reduces the pressure inside the reaction chamber via a reaction chamber exhaust port provided in the reaction chamber.

9. The measuring device according to claim 8, further comprising a reaction chamber intake section provided in the reaction chamber for introducing outside air into the reaction chamber, the intake section having a higher intake resistance than a reaction chamber exhaust port that connects the reaction chamber to the reaction chamber exhaust section.

10. The measuring device according to claim 9, further comprising a measurement chamber intake section having a higher intake resistance than the reaction chamber exhaust port and provided for introducing outside air into the measurement chamber.

11. The measuring device according to claim 10, wherein the reaction chamber intake section has a higher intake resistance than the measurement chamber intake section.

12. A measuring device according to any one of claims 8 to 11, further comprising a reaction chamber housing that constitutes the reaction chamber and a measurement chamber housing that constitutes the measurement chamber, wherein the reaction chamber housing and the measurement chamber housing share a partition wall in which the inter-chamber communication port that connects the reaction chamber and the measurement chamber is provided.

13. A measuring device according to any one of claims 8 to 12, wherein the measurement chamber further comprises an optical scanning system that scans the primary light onto the array plate, and an optical detection system that detects secondary light emitted from the array plate in response to irradiation with the primary light.

14. A measuring device according to any one of claims 8 to 13, wherein a reaction chamber housing constituting the reaction chamber and a measurement chamber housing constituting the measurement chamber are electrically conductive and commonly grounded.

15. A measuring device as described in any one of claims 8 to 14, further comprising an access port for inserting and removing the plate unit into and from the reaction chamber, and a port closure part for opening and closing the access port, wherein the port closure part is grounded via a reaction chamber housing that constitutes the reaction chamber and in which the access port is provided.

16. The measurement device of claim 15, wherein the access port is closed by the port closure via a sealing member that is conductive and elastic.

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