Sample Dispensing Device

Abstract

To provide a sample dispenser capable of keeping humidity around liquid droplets formed on sensor chips at a level that does not allow the droplets to dry up without having to separately provide a humidifier such as an ultrasonic atomizer.SOLUTION: A sample dispenser is provided, comprising an installation unit having sensor chips installed therein, a dispensing unit for forming liquid droplets on the sensor chips, a housing having a dispensing space formed therein for accommodating the installation unit and the dispensing unit, and a water storage unit disposed in the dispensing space.SELECTED DRAWING: Figure 2

Description

Technical Field

[0001] The present invention relates to a sample dispensing device.

Background Art

[0002] For example, in a detection method such as surface plasmon resonance for detecting the interaction of biomolecules, various substances (analytes) are supplied onto a sensor chip on which biomolecules are immobilized, and the interaction between the biomolecules and the analyte on the sensor chip is detected. In order to immobilize the biomolecules on the sensor chip, a sample dispensing device that forms fine droplets containing the biomolecules on the sensor chip is used.

[0003] If the droplet containing the biomolecules formed on the sensor chip dries before detecting the interaction with the analyte, the biomolecules may not bind sufficiently to the sensor chip, the concentration of the biomolecules inside the droplet may be uneven, or the immobilization density of the biomolecules on the sensor chip may change, resulting in unstable detection results. Therefore, in order to protect the droplets formed on the sensor chip from drying, as described in Patent Document 1, a sample dispensing device equipped with an ultrasonic nebulizer or the like that humidifies the entire internal space of the sample dispensing device has been considered.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] An object of the present invention is to provide a sample dispensing device that can keep the humidity around the droplets formed on the sensor chip at a humidity at which the droplets do not dry without separately providing an ultrasonic nebulizer or the like.

Means for Solving the Problem

[0006] That is, the sample dispensing device according to the present invention includes an installation part for installing a sensor chip, a dispensing part for forming droplets on the sensor chip, a housing in which a dispensing space for accommodating the installation part and the dispensing part is formed, and a water storage part disposed inside the dispensing space.

[0007] According to such a sample dispensing device, since the water storage part is formed in the dispensing space, the humidity in the dispensing space can be maintained at a humidity at which the droplets formed on the sensor chip do not dry without separately providing a humidifying device such as an ultrasonic nebulizer. As a result, the detection result of the interaction using this sensor chip can be stabilized and the detection accuracy can be improved.

[0008] In order to keep the humidity near the sensor chip higher, it is preferable that the installation part is a stage having an installation surface for installing the sensor chip, and a space forming member is further provided which is arranged so as to cover at least a part of this stage and forms an installation space for accommodating the installation surface and the water storage part between the stage. In this case, it is preferable that the dispensing part is arranged outside the installation space, and an opening for forming droplets on the sensor chip from the outside of the installation space is formed in the space forming member.

[0009] If a plurality of installation parts are provided on the stage, biomolecules can be continuously fixed to a plurality of sensor chips.

[0010] From the viewpoint of simplifying the replenishment of water to the water storage part, it is preferable that the water storage part is an integral one. In order to suppress the adhesion of dirt or the like inside the water storage part, it is preferable to simplify the shape of the water storage part. From such a viewpoint, it is preferable that the water storage part is arranged so as to surround the installation surface from the outside.

[0011] As a specific embodiment of the present invention, an example is that the water storage part is a groove formed in the installation part.

[0012] If the space forming member is transparent, it is preferable because it is possible to visually confirm whether droplets are normally formed on the sensor chip while the space forming member is placed on the stage.

Advantages of the Invention

[0013] According to the present invention, without separately providing an ultrasonic nebulizer or the like, the humidity around the droplets can be maintained at a humidity at which the droplets do not dry, so that while significantly suppressing the manufacturing cost of the sample dispensing device compared to the conventional case, the detection accuracy of the interaction can be sufficiently maintained. In addition, since there is no need for a space for arranging an ultrasonic nebulizer or the like, the sample dispensing device can be made smaller than the conventional one.

Brief Description of the Drawings

[0014]

Figure 1

Figure 2

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Mode for Carrying Out the Invention

[0015] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. The sample dispensing device 100 according to this embodiment includes, for example, as shown in FIGS. 1 and 2, a sample storage unit 1 for storing a sample before dispensing, an installation unit 2 on which a sensor chip C on which droplets D are formed on the surface when the sample is dispensed is placed, a dispensing unit 3 for dispensing a sample onto the surface of the sensor chip C installed in the installation unit 2 to form droplets D, and a housing 4 that houses these inside.

[0016] The sample storage unit 1 includes, for example, a positioning member (not shown) for positioning a container such as a microplate in which a large number of recesses capable of storing a plurality of types of samples are formed at a predetermined installation position.

[0017] The installation unit 2 is, for example, a stage 2 on which an installation surface 21 for installing the sensor chip C is formed on its surface. This stage 2 is, for example, a block-shaped one formed of a metal or resin containing an alloy, and the installation surface 21 is, for example, a recess formed on the upper surface of the stage 2 that serves this role. In this embodiment, four installation surfaces 21 are provided so as to surround the center of the stage 2 so that four sensor chips C can be held on one stage 2 at a time.

[0018] The dispensing unit 3 includes, for example, a droplet forming unit 31 that collects the sample installed in the sample storage unit 1 and forms droplets D on the sensor chip C, a moving means 32 that moves the droplet forming unit 31 between the sample storage unit 1 and the sensor chip C, and a control unit 33 that controls the moving means 32.

[0019] The droplet forming unit 31 is, for example, a rod-shaped one with a diameter of the tip portion of about 0.1 mm to 1.0 mm. The moving means 32 includes, for example, a holding unit that holds the droplet forming unit 31, a rail disposed between the sample storage unit 1 and the stage 2, and a driving unit for moving the holding unit along the rail.

[0020] The control unit 33 controls the movement of the holding unit on the rail, for example, by issuing commands to the drive unit. Specifically, it is an information processing circuit comprising a digital circuit composed of a CPU, memory, communication ports, etc., an analog circuit equipped with buffers, amplifiers, etc., and AD converters, DA converters, etc. that mediate between these digital and analog circuits. Then, the CPU and its peripheral devices cooperate according to a predetermined program stored in the memory, and this information processing circuit exhibits the function of the control unit.

[0021] This information processing circuit may be composed of, for example, an information processing device 331 such as a general-purpose PC arranged outside the housing and a circuit board 332 arranged inside the housing, as shown in FIG. 2. Further, a display 333 for displaying, for example, the operating status of the sample dispensing device may be connected to the information processing circuit. The sample dispensing device 100 may further include a power supply unit 34 that supplies power to these moving means 32, control unit 33, etc.

[0022] The housing 4 houses the sample storage unit 1, installation unit 2, and dispensing unit 3 inside, and a dispensing space A where the sample is dispensed is formed inside. For example, by closing the openable and closable door 41, the dispensing space A can be made into an airtight closed space.

[0023] Thus, the sample dispensing device 100 according to this embodiment further includes a water storage unit 5 provided inside the dispensing space A.

[0024] The water storage unit 5 is, for example, a storage unit having a storage space for storing water inside and a water vapor discharge port for discharging water vapor generated from the water stored inside the storage space to the outside of the storage space. In this embodiment, as shown in FIGS. 2 and 3, the groove 5 formed on the upper surface of the stage 2 serves this role. This groove 5 is formed, for example, so as to surround the above-described installation surface 21 from its periphery and is integrally connected as a whole. More specifically, the groove 5 is an annular one formed such that the entire inner peripheral surface thereof is smoothly connected using a curved surface without interruption in the middle.

[0025] As shown in FIGS. 2 to 4, the sample dispensing device 100 according to the present embodiment further includes a space forming member 6 that forms an installation space B for accommodating the installation surface 21 and the water storage portion 5 therein. More specifically, the space forming member 6 is, for example, a transparent lid body 6 that is disposed so as to cover the stage 2 and forms the installation space B between the stage 2.

[0026] In the present embodiment, as shown in FIG. 2, the dispensing unit 3 and the sample storage unit 1 are disposed outside the installation space B formed between the lid body 6 and the stage 2. Therefore, as shown in FIGS. 2 to 4, an opening 61 having a size that allows the droplet forming portion 31 of the dispensing unit 3 disposed outside the installation space B to access the surface of the sensor chip C disposed on the stage 2 is formed in the lid body 6.

[0027] The sample dispensing device 100 further includes a humidity sensor 7 for monitoring the humidity inside the installation space B. In the present embodiment, as shown in FIGS. 4 and 5, the humidity sensor 7 is disposed on the upper surface of the stage 2 and at the central portion of the stage 2 surrounded by the above-described four installation surfaces 21. The sample dispensing device 100 may, for example, also include a sensor control unit for controlling the humidity sensor 7. This sensor control unit may be, for example, the above-described information processing circuit that performs its function.

[0028] The procedure and method for dispensing a sample onto the sensor chip C by the sample dispensing device 100 configured as described above are as follows. First, place the sensor chip C on the installation surface 21 on the stage 2. After injecting water into the groove 5 which is the water storage part 5, place the lid 6 that covers the stage 2. Next, place the sample to be dispensed in the sample storage part 1, close the opening / closing door 41 of the housing 4, and input a signal for starting dispensing to the sample dispenser 100.

[0029] Upon receiving the signal for starting dispensing, the control unit moves the droplet formation part 31 by the moving means 32, collects the sample in the droplet formation part 31, and forms minute droplets D of about 1 nl to 50 nl, for example, on the surface of the sensor chip C installed on the installation surface 21 on the stage 2. At this time, the droplet formation part 31 accesses the sensor chip C through the opening 61 formed in the lid 6 and forms the droplet D by dropping the sample. After forming the droplet D, the droplet formation part 31 is washed with a cleaning liquid such as ethanol, for example, and then returned to the original standby position by the moving means 32 again.

[0030] According to the sample dispenser 100 configured as described above, since the water storage part 5 is provided on the upper surface of the stage 2 in the dispensing space, the humidity in the dispensing space A, particularly the humidity in the vicinity of the sensor chip C, can be maintained high with a simple configuration without separately providing a humidifying device such as an ultrasonic nebulizer. As a result, the minute droplets D formed on the sensor chip C can be protected from drying. Also, since the groove 5 which is the water storage part 5 is formed on the upper surface of the stage 2, the sample dispenser 100 can be made smaller compared to the case where the water storage part 5 is separately arranged outside the stage 2.

[0031] Since the dispensing part 3 and the sample storage part 1 are arranged outside the installation space B formed between the lid 6 and the stage 2, the volume of the installation space B can be made as small as possible. As a result, only the humidity in the vicinity of the sensor chip C can be efficiently maintained.

[0032] Since the water storage part 5 is the groove 5, the breeding of miscellaneous bacteria and the like can be suppressed compared to the case where a sponge or the like is used as the water storage part 5, for example.

[0033] If the grooves 5 are connected in series, water can be distributed throughout the grooves 5 by injecting water from one location of the grooves 5, so that the water replenishment work is simple. For example, the grooves 5 can store an amount of water (e.g., 10 ml to 100 ml) necessary to maintain the humidity in the space overnight. However, when starting a new dispensing operation or replenishing water midway, even with the stage 2 set inside the housing 4, water can be easily replenished using a dropper or the like.

[0034] Since the groove 5 is an annular shape in which the entire inner circumferential surface is a curved surface and is smoothly connected, the locations where water stagnates can be reduced as much as possible, and the dirt inside the groove 5 due to the growth of miscellaneous bacteria and the like can be suppressed.

[0035] Since the lid body 6 is transparent, it is possible to check whether the liquid droplets D are being formed normally even with the lid body 6 closed. Also, it is possible to check the remaining amount of water in the groove 5 even with the lid body 6 closed.

[0036] Since the humidity sensor 7 is disposed at the center of the stage 2 surrounded by the plurality of installation surfaces 21, the humidity in the installation space B can be measured. As a result, the humidity in the vicinity of the sensor chip C can be monitored more accurately.

[0037] The present invention is not limited to the above-described embodiment. For example, the grooves are not limited to being installed so as to surround the entire plurality of installation surfaces from the outside, and may be installed so as to surround each installation surface one by one, or may be installed between each installation surface.

[0038] The water storage part is not limited to the groove as described above, and includes one or more storage spaces for storing water inside and a water vapor discharge port for discharging water vapor from within this storage space. For example, it may be a container formed separately from the stage, such as a bottomed hole formed in the stage, a water receiving tray, etc., or a porous body such as a sponge. Furthermore, it may be a jelly-like substance that holds water inside and can release it as water vapor from the surface.

[0039] In the above-described embodiment, the case where the water storage part is arranged inside the installation space has been described. However, it is not limited to this, and it may be arranged in the dispensing space where the installation part and the dispensing part are arranged. Inside the housing, separately from the above-described dispensing space, there may be provided a machine room or the like for accommodating an additional humidifying mechanism and other devices.

[0040] The openings formed in the space forming member may be appropriately changed according to the number of sensor chips installed on the installation surface on the stage and the locations where droplets are formed. Also, it is preferable that these openings can be opened and closed as necessary. This opening and closing may be manually performed by a human, or an opening and closing part may be provided and automatically controlled so that the openings are in an open state only when the droplet forming part approaches. In the above-described embodiment, the case where the space forming member covers the entire installation part (stage) has been described. However, the space forming member only needs to cover at least a part of the installation part.

[0041] The sample dispensing device may further include a water replenishing device for automatically replenishing water to the water storage part.

[0042] A coating layer for water repellency and antibacterial purposes may be further formed on the surface of the stage. When the water storage part is a groove, a bottomed hole, a container, etc., it is preferable that this coating layer is also formed inside these. Such a coating layer can be formed, for example, by applying a coating composition containing a water repellent or an antibacterial agent to the stage surface by spin coating, dip coating, roll coating, spray coating, gravure coating, nozzle coating, etc. so as to have a thickness of 0.1 μm or more and 500 μm or less, and then curing it. Specific examples of the coating composition include, for example, a resin composition containing a fluorine compound as the water repellent, a resin composition containing silver ions as the antibacterial agent, and the like.

[0043] The installation part does not necessarily have to be a stage as described above, and for example, it may be one having an installation surface formed on the inner surface of the housing.

[0044] The sample dispensing device according to the present invention is not limited to one that dispenses a biopolymer used for surface plasmon resonance or the like onto a sensor chip, and may be used to form droplets for other applications that dislike rapid drying. In addition, various modifications and combinations of embodiments may be made as long as they do not depart from the gist of the present invention.

Example

[0045] Hereinafter, experimental examples using the sample dispensing device 100 according to the present invention will be described, but it goes without saying that the present invention is not limited to the examples described herein. Experimental Example 1 First, regarding the sample dispensing device 100 according to the present invention, by storing water in the water storage part 5 provided inside the dispensing space A, it was confirmed that the humidity near the sensor chip C can be kept constant at a high level without providing an ultrasonic nebulizer.

[0046] <Experimental method> As described in the above embodiment, a stage 2 having a groove 5 formed on its upper surface was attached to the sample dispensing device 100. The humidity in the installation space B was measured by a humidity sensor 7 (TDK, CHS-UGR) arranged at the center of the stage 2 when water was not contained in the groove 5 (hereinafter also referred to as the case without water) and when 15 ml of pure water was contained (hereinafter also referred to as the case with water). When this experiment was conducted, the room temperature in the laboratory was 23.1 °C and the humidity in the laboratory was 52.3%RH.

[0047] In addition, in this embodiment, as described in the above embodiment, since four sensor chips C can be arranged on one stage 2, four openings 61 are formed in the lid body 6 which is the space forming member 6 at positions corresponding to the installation surfaces 21 of these sensor chips C. Also, one opening 61 is formed at a position directly above the humidity sensor 7 arranged on the stage 2. Therefore, the humidity on the stage 2 when the openings 61 were opened and closed in the case with water was also measured. Fig. 6 shows diagrams respectively showing the opening and closing states of the openings 61 in the case without water (experiment number 1) and in the case with water (experiment numbers 2 to 8).

[0048] Fig. 7 shows the change over time of the output value from the above-described humidity sensor 7, and the average humidity is shown in Table 1 below. The converted humidity (%) in Table 1 can be obtained by multiplying the average output value (V) of the humidity sensor 7, which has already been confirmed by experiments to be such that the output average voltage value (0V to 1V) corresponds to the converted humidity (0% to 100%), by 100. The upper limit value of the converted humidity in Table 1 was set to 100%.

[0049]

Table 1

[0050] <Considerations on the measurement results> From the results of FIG. 7 and Table 1, compared with the case without water (Experiment No. 1), in the case with water (Experiment Nos. 2 to 8), the humidity near the sensor chip C is stably higher. Even without an ultrasonic nebulizer or the like as in the conventional case, the humidity is sufficient to prevent the droplets D formed on the sensor chip C from drying, and it was confirmed that this humidity is kept constant.

[0051] Also, it was confirmed that by opening and closing the opening 61 formed in the lid body 6 as needed, the desired humidity can be maintained. Note that the humidity in the laboratory when this experiment was conducted was 52.3%RH, which was equal to the converted humidity in the installation space B in the case without water (1). Therefore, it can be said that the accuracy of humidity measurement in this experiment is reliable.

[0052] Experimental Example 2 In Experimental Example 1, it was confirmed that the humidity near the sensor chip C could be stably kept high for about one hour of use. In this Experimental Example 2, the humidity change on the stage 2 was measured for a longer time to confirm whether the humidity was stably maintained.

[0053] <Experimental Method> Using the same sample dispensing device 100 as in Experimental Example 1, pure water was poured into the groove 5 formed on the stage 2 until it was full. At this time, the amount of water contained in the groove 5 was approximately 40 ml. In this state, the humidity in the installation space B was continuously measured by a humidity sensor 7 (TDK, CHS-UGR) arranged at the center of the stage 2. The room temperature in the laboratory when this experiment was conducted was 24.3°C. The results are shown in FIG. 8. The upper graph in FIG. 8 shows the results measured from the start of measurement to 2000 seconds, and the lower graph shows the results from the start of measurement to 8 hours later. Note that the two graphs in FIG. 8 were obtained at different times.

[0054] <Consideration of Experimental Results> From the results of Fig. 8, it was confirmed that the humidity on stage 2 reached near the maximum value approximately 800 seconds after water was set on stage 2, and the humidity was kept constant until 8 hours had elapsed thereafter. From these results, it was found that if about 40 ml of water was put into the groove 5 on stage 2, the humidity in the vicinity of the sensor chip C could be kept high and constant for 8 hours or more. Therefore, it is considered that as long as a sufficient amount of water is put in, even when the sample dispensing device 100 is operated overnight, the droplet D formed on the sensor chip C can be kept without drying.

Explanation of symbols

[0055] 100 ··· Sample dispensing device 1 ··· Sample storage section 2 ··· Installation section (stage) 21 ··· Installation surface 3 ··· Dispensing section 4 ··· Housing A ··· Dispensing space 5 ··· Water storage section (groove) 6 ··· Space forming member (lid) B ··· Installation space C ··· Sensor chip D ··· Droplet

Claims

1. An installation part for installing a sensor chip, a dispensing part for forming a liquid droplet on the sensor chip, a housing having a dispensing space formed therein for housing the installation part and the dispensing part, and a water storage part disposed inside the dispensing space, wherein the installation part is a stage having an installation surface for installing the sensor chip, and the water storage part is a groove formed on the upper surface of the stage, and a sample dispensing device characterized by this.

2. The sample dispensing device according to claim 1, wherein the water storage part is disposed so as to surround the installation surface from the outside.

3. The installation part is disposed so as to cover at least a part of the stage, and further includes a space forming member that forms an installation space for housing the installation surface and the water storage part inside between the stage, and the sample dispensing device according to claim 1 or 2.

4. The dispensing part is disposed outside the installation space, and an opening for forming a liquid droplet on the sensor chip from the outside of the installation space is formed in the space forming member, and the sample dispensing device according to claim 3.

5. The sample dispensing device according to any one of claims 1 to 4, wherein a plurality of the installation surfaces are formed on the stage.

6. The sample dispensing device according to any one of claims 1 to 5, wherein the water storage part is a continuous one.

7. The sample dispensing device according to claim 3, wherein the space forming member is transparent.

8. In a sample dispensing device including an installation part for installing a sensor chip, a dispensing part for forming a liquid droplet on the sensor chip, a housing having a dispensing space formed therein for housing the installation part and the dispensing part, and a water storage part disposed inside the dispensing space, wherein the installation part is a stage having an installation surface for installing the sensor chip, and the water storage part is a groove formed on the upper surface of the stage, thereby a humidity maintaining method for maintaining the humidity of the dispensing space.

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