Analytical apparatus and analytical method

Abstract

The goal is to reduce the influence of the size of the generated droplets on the measurement results regarding the target substance. [Solution] The analytical apparatus according to the embodiment is an analytical apparatus that performs analysis of a target substance contained in a sample by moving a droplet by applying an electric field, and comprises a droplet generation means, a first measuring means, a second measuring means, and an analysis means. The droplet generation means generates a droplet to be used for the analysis. The first measuring means measures the size of the droplet. The second measuring means performs measurements of the target substance using the droplet. The analysis means analyzes the amount of the target substance in the sample based on the measured size of the droplet and the results of the measurements of the target substance.

Description

Technical Field

[0001] The embodiments disclosed in this specification and the drawings relate to an analyzer and an analysis method.

Background Art

[0002] Conventionally, Digital Micro Fluidics (DMF) technology that can manipulate droplets on a substrate using an electrical signal has been known. According to DMF technology, for example, based on the principle called electro-wetting on dielectric, it is possible to manipulate droplets on a conductive substrate by applying an electric field according to an electrical signal. Due to the free operability of the droplets and the small reaction volume, DMF technology has been applied to Point of Care Testing (POCT) applications and the improvement of the efficiency of biological analysis reactions.

[0003] When applying DMF technology to quantitative analysis such as biochemical tests and biological sample analysis, the accuracy of dispensing samples and reagents becomes an issue. However, since patient specimens used as samples have different compositions and physical properties for each patient, it is difficult to dispense droplets reproducibly in DMF technology. If the dispensing of droplets containing samples or reagents fails for some reason, using the droplets as they are for measurement may reduce the accuracy of test values. For example, if there is too much or too little sample relative to the reagent, there is a risk that the amount of the target substance in the sample cannot be accurately analyzed.

Prior Art Documents

Patent Documents

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] One of the problems that the embodiments disclosed herein and in the drawings aim to solve is to reduce the influence of the size of the generated droplets on the measurement results regarding the target substance. However, the problems that the embodiments disclosed herein and in the drawings aim to solve are not limited to the above problem. Problems corresponding to the effects of each configuration shown in the embodiments described later can also be positioned as other problems. [Means for solving the problem]

[0006] The analytical apparatus according to this embodiment is an analytical apparatus that performs analysis of a target substance contained in a sample by moving a droplet by applying an electric field, and comprises a droplet generation means, a first measuring means, a second measuring means, and an analysis means. The droplet generation means generates a droplet to be used for the analysis. The first measuring means measures the size of the droplet. The second measuring means performs measurements of the target substance using the droplet. The analysis means analyzes the amount of the target substance in the sample based on the measured size of the droplet and the results of the measurements of the target substance. [Brief explanation of the drawing]

[0007] [Figure 1] A block diagram showing an example configuration of the analytical apparatus according to the first embodiment. [Figure 2] A schematic plan view showing an example of the configuration of a fluid device in an analytical apparatus according to the first embodiment. [Figure 3] A cross-sectional view showing an example of the configuration of a fluid device in an analytical apparatus according to the first embodiment. [Figure 4] A cross-sectional view showing an example of the configuration of the sample droplet generation unit in the analytical apparatus according to the first embodiment. [Figure 5] A cross-sectional view showing another example of the configuration of the sample droplet generation section in the analytical apparatus according to the first embodiment. [Figure 6] A cross-sectional view showing an example of the configuration of the first reagent droplet generation unit in the analytical apparatus according to the first embodiment. [Figure 7] A cross-sectional view showing an example of the configuration of the second reagent droplet generation unit in the analytical apparatus according to the first embodiment. [Figure 8]A cross-sectional view showing an example of the configuration of the second measuring unit in the analytical apparatus according to the first embodiment. [Figure 9] A cross-sectional view showing another configuration example of the second measuring section in the analytical apparatus according to the first embodiment. [Figure 10] A flowchart showing an example of operation of the analytical apparatus according to the first embodiment. [Figure 11] A schematic plan view showing an example of operation of the analytical apparatus according to the first embodiment. [Figure 12] A schematic plan view showing an example of operation of the analytical apparatus according to the first embodiment. [Figure 13] A schematic plan view showing an example of the configuration of a fluid device in an analytical apparatus according to Modification 1 of the First Embodiment. [Figure 14] A schematic plan view showing an example of the configuration of a fluid device in an analytical apparatus according to a modified example 2 of the first embodiment. [Figure 15] A schematic plan view showing an example of the configuration of a fluid device in an analytical apparatus according to a modified example 3 of the first embodiment. [Figure 16] A schematic plan view showing an example of the configuration of a fluid device in an analytical apparatus according to a modified example 4 of the first embodiment. [Figure 17] A flowchart showing an example of operation of the analytical apparatus according to Modification 5 of the First Embodiment. [Figure 18] A schematic plan view showing an example of operation of an analytical apparatus according to Modification 5 of the First Embodiment. [Figure 19] Figure 18 is followed by a schematic plan view showing an example of operation of the analytical apparatus according to Modification 5 of the First Embodiment. [Figure 20] Figure 18 is followed by a schematic plan view showing an example of operation of the analytical apparatus according to Modification 5 of the First Embodiment. [Figure 21] Figure 20 is followed by a schematic plan view showing an example of operation of the analytical apparatus according to Modification 5 of the First Embodiment. [Figure 22] A block diagram showing an example configuration of the analytical apparatus according to the second embodiment. [Figure 23] A schematic plan view showing an example of the configuration of a fluid device in an analytical apparatus according to the second embodiment. [Figure 24]Flowchart showing an operation example of the analyzer according to the second embodiment. [Figure 25] Schematic diagram for explaining contamination in the analyzer according to the second embodiment. [Figure 26] Block diagram showing a configuration example of the analyzer according to the third embodiment. [Figure 27] Schematic plan view showing a configuration example of the fluid device in the analyzer according to the third embodiment. [Figure 28] Block diagram showing a configuration example of the analyzer according to the fourth embodiment. [Figure 29] Schematic plan view showing a configuration example of the fluid device in the analyzer according to the fourth embodiment. [Figure 30] Block diagram showing a configuration example of the analyzer according to the fifth embodiment. [Figure 31] Schematic plan view showing a configuration example of the fluid device in the analyzer according to the fifth embodiment. [Figure 32] Block diagram showing a configuration example of the analyzer according to the sixth embodiment. [Figure 33] Flowchart showing an operation example of the analyzer according to the sixth embodiment.

Embodiments for Carrying Out the Invention

[0008] Hereinafter, embodiments of the analyzer and the analysis method will be described with reference to the drawings. In the following description, components having substantially the same functions and configurations will be denoted by the same reference numerals, and duplicate explanations will be made only when necessary.

[0009] (First Embodiment) Figure 1 is a block diagram showing an example configuration of the analytical apparatus 1 according to the first embodiment. The analytical apparatus 1 is an analytical apparatus that performs analysis of a target substance contained in a sample by moving a droplet by applying an electric field. For the movement of the droplet, for example, electrowetting on a dielectric is used. Electrowetting on a dielectric is a method of moving a droplet on a dielectric by changing the wettability of the droplet by applying an electric field. In the following description, "electrowetting on a dielectric" will be simply referred to as "electrowetting".

[0010] As shown in Figure 1, the analysis apparatus 1 according to this embodiment includes, for example, a fluid device 2, a fluid input / output unit 3, a processing circuit 4, and an output interface 5.

[0011] Fluid device 2 is a DMF device based on digital microfluidic (DMF) technology. Specifically, fluid device 2 is equipped with multiple electrodes and uses electrowetting to perform operations such as droplet dispensing, movement, mixing, stirring, and standing. In the following description, droplet dispensing may also be referred to as droplet "generation."

[0012] The fluid device 2 includes, for example, a droplet generation unit 21, a first measurement unit 22, a second measurement unit 23, a waste liquid unit 24, and a cleaning liquid introduction unit 25. Each part of the fluid device 2 is arranged to correspond to one or more electrodes among the electrodes provided by the fluid device 2.

[0013] The droplet generation unit 21 generates droplets used for the analysis of the target substance described above. The droplet generation unit 21 is composed of, for example, a holding unit that holds a certain amount of liquid containing a sample or reagent, and one or more electrodes near the holding unit. The holding unit is also called a reservoir. Droplet generation is performed, for example, by dividing a portion of the liquid held in the holding unit into droplets using electrowetting. The droplet generation unit 21 is an example of a droplet generation means in this embodiment.

[0014] The droplet generation unit 21 includes, for example, a sample droplet generation unit 211, a first reagent droplet generation unit 212, and a second reagent droplet generation unit 213.

[0015] The sample droplet generation unit 211 generates sample droplets containing the sample. The sample is, for example, a test sample such as blood collected from a living body such as a patient, or a standard sample for generating standard data. The sample droplet generation unit 211 is an example of a sample droplet generation means in this embodiment.

[0016] The first reagent droplet generation unit 212 and the second reagent droplet generation unit 213 each generate reagent droplets containing reagents used for analysis of a target substance. The first reagent droplet generation unit 212 and the second reagent droplet generation unit 213 are examples of reagent droplet generation means in this embodiment.

[0017] More specifically, the first reagent droplet generation unit 212 generates a first reagent droplet containing the first reagent of the two-reagent system. The first reagent reacts with predetermined components, such as target substances, contained in the standard sample and the test sample. The first reagent is, for example, a buffer solution containing bovine serum albumin (BSA).

[0018] Furthermore, the second reagent droplet generation unit 213 generates a second reagent droplet containing the second reagent, which is paired with the first reagent in the two-reagent system. The second reagent is a solution containing a predetermined antigen or antibody contained in the sample, and an insoluble carrier on which an antigen or antibody that binds or dissociates by a specific antigen-antibody reaction is immobilized, such as carrier particles. The antigen or antibody that binds or dissociates by the specific reaction may be an enzyme, substrate, aptamer, or receptor.

[0019] In the above description, we have described the case in which the fluid device 2 has two reagent droplet generation units and uses a two-reagent system. However, the fluid device 2 may have one reagent droplet generation unit and use one reagent. Furthermore, the droplet generation unit 21 may be composed of at least one of the sample droplet generation unit 211, the first reagent droplet generation unit 212, and the second reagent droplet generation unit 213.

[0020] Furthermore, the droplet generation unit 21 may include a mechanism for introducing an immiscible liquid that does not mix with the sample or reagent when generating droplets from a liquid containing the sample or reagent. For example, the droplet generation unit 21 dispenses the sample droplet or reagent droplet so that it is contained within a droplet containing the immiscible liquid. The immiscible liquid has components that prevent the leakage of components from the sample or reagent. An example of an immiscible liquid is a fluorinated solvent. Examples of fluorinated solvents include hydroxyfluoroether (HFE) and FC-40. By dispensing the sample droplet or reagent droplet into a droplet containing the immiscible liquid in this way, it is possible to prevent evaporation of the sample droplet or reagent droplet or improve the liquid separation of these droplets. In addition, a surfactant may be mixed in when dispensing the sample droplet or reagent droplet into a droplet containing the immiscible liquid.

[0021] The first measuring unit 22 measures the size of the droplets generated by the droplet generation unit 21. The size of the droplet is, for example, the diameter, area, volume, and impedance of the droplet. In this embodiment, the first measuring unit 22 includes an image acquisition unit that acquires an image of the droplet. The image acquisition unit is, for example, an image sensor such as an optical camera. For example, the first measuring unit 22 acquires the diameter, shape, or area of ​​the droplet in the image from the acquired two-dimensional image of the droplet. Then, the first measuring unit 22 calculates the volume of the droplet using information such as the diameter of the droplet and the height and width of the flow path of the fluid device 2. The first measuring unit 22 may also estimate the volume of the droplet based on data acquired in advance using, for example, a sample droplet containing a standard sample. At least one of the acquisition of the diameter of the droplet and the calculation of the volume may be performed by the processing circuit 4. The first measuring unit 22 is an example of the first measuring means in this embodiment.

[0022] In this embodiment, the first measuring unit 22 measures the size of the sample droplets generated by the sample droplet generation unit 211, the size of the first reagent droplets generated by the first reagent droplet generation unit 212, and the size of the second reagent droplets generated by the second reagent droplet generation unit 213. However, if the size of the droplets does not vary significantly with each dispensing, measurement by the first measuring unit 22 may be omitted for some droplets. For example, if the size of the first reagent droplets does not vary significantly with each dispensing, measurement by the first measuring unit 22 may be omitted for the first reagent droplets.

[0023] The second measurement unit 23 performs measurements on a target substance using droplets generated by the droplet generation unit 21. The target substance may be, for example, nucleic acids, proteins, endocrine substances, cells, blood cells, viruses, microorganisms, organic compounds, inorganic compounds, or low-molecular-weight compounds. As a measurement of the target substance, the second measurement unit 23 performs at least one of the following: optical measurement, electrochemical measurement, and hue measurement of the droplet. In this embodiment, the second measurement unit 23 is an optical measurement unit that performs optical measurements on the droplet. In this case, the second measurement unit 23 is equipped with, for example, a spectrometer to measure the transmittance, absorbance, fluorescence intensity, bioluminescence intensity, chemiluminescence intensity, scattered light intensity, etc., of the droplet. In optical measurement, any measurement method can be used depending on the sample and reagents, such as endpoint analysis, time-dependent analysis, or initial velocity analysis. The second measurement unit 23 is an example of a second measurement means in this embodiment.

[0024] The waste liquid unit 24 discards droplets within the fluid device 2. For example, the waste liquid unit 24 discards droplets if the size of the droplet measured by the first measuring unit 22 is determined to be outside the specified range. The waste liquid unit 24 also discards droplets after measurement by the second measuring unit 23 has finished.

[0025] The cleaning solution introduction unit 25 introduces a cleaning solution for cleaning the fluid device 2, which has been contaminated by droplet manipulation. The cleaning solution is, for example, pure water, an alkaline detergent, or an acidic detergent. The introduced cleaning solution is delivered to each part of the fluid device 2, for example, along the flow path shown by the solid line in Figure 1. This allows the surface of the fluid device 2, for example, the surfaces of the hydrophobic layer 64 and hydrophobic layer 67 described later, to be cleaned. The cleaning solution introduction unit 25 generates the cleaning solution in the form of droplets. In this case, the droplets containing the cleaning solution are delivered to each part of the fluid device 2 using electrowetting, and each part of the fluid device 2 is cleaned. Alternatively, the cleaning solution introduction unit 25 may introduce running water containing the cleaning solution from the cleaning solution introduction unit 25. In this case, each part of the fluid device 2 is cleaned by the cleaning solution introduction unit 25 continuously or intermittently delivering the cleaning solution.

[0026] The fluid input / output unit 3 performs fluid input and output to the fluid device 2. The fluid input / output unit 3 includes, for example, a sample introduction unit 31, a reagent storage unit 32, a waste liquid tank unit 33, and a cleaning liquid storage unit 34.

[0027] The sample introduction unit 31 introduces the sample to be used in the fluid device 2. The sample introduction unit 31 is connected to the sample droplet generation unit 211. For example, a sample container for containing the sample is placed in the sample introduction unit 31. The sample introduction unit 31 also includes, for example, a probe for introducing the sample from this sample container to the sample droplet generation unit 211.

[0028] The reagent storage unit 32 stores reagents such as the first reagent and the second reagent. The reagent storage unit 32 is connected to the first reagent droplet generation unit 212 and the second reagent droplet generation unit 213. The reagent storage unit 32 is equipped with, for example, a first reagent bottle for containing the first reagent and a second reagent bottle for containing the second reagent. The reagent storage unit 32 also includes, for example, arms for moving the first reagent bottle and the second reagent bottle to the first reagent droplet generation unit 212 and the second reagent droplet generation unit 213, respectively.

[0029] The waste liquid tank section 33 is connected to the waste liquid section 24 and collects the waste liquid gathered in the waste liquid section 24. The waste liquid tank section 33 is equipped with, for example, a probe for sucking up the waste liquid collected in the waste liquid section 24. The waste liquid tank section 33 is also equipped with, for example, a waste liquid bottle for collecting the waste liquid.

[0030] The cleaning solution storage unit 34 is connected to the cleaning solution introduction unit 25 and stores the cleaning solution that will be introduced into the fluid device 2 from the cleaning solution introduction unit 25. For example, a cleaning solution bottle for containing the cleaning solution is placed in the cleaning solution storage unit 34. The cleaning solution storage unit 34 is also equipped with a probe for introducing the cleaning solution from the cleaning solution bottle into the cleaning solution introduction unit 25. The cleaning solution storage unit 34 may be omitted. In this case, for example, the cleaning solution bottle is placed in the reagent storage unit 32, and the reagent storage unit 32 is also connected to the cleaning solution introduction unit 25.

[0031] The processing circuit 4 is a control circuit that performs overall control of the analysis device 1, and also an arithmetic circuit that performs various calculations. In this embodiment, the processing circuit 4 includes a control function 41, a determination function 42, and an analysis function 43. The dotted line in Figure 1 represents an example of a signal path from the processing circuit 4.

[0032] The control function 41 is a function that comprehensively controls each part of the analyzer 1. The control function 41 is connected to, for example, the fluid device 2 and performs droplet manipulation using electrowetting. Specifically, the control function 41 manipulates droplets on the electrodes by controlling the voltage applied to each of the multiple electrodes provided by the fluid device 2. Droplet manipulation may be performed according to a program stored in a memory circuit (not shown), or it may be performed by a user such as a physician or medical technologist via an input interface (not shown). Furthermore, the control function 41 controls a drive mechanism (not shown) to introduce the sample, the first reagent, and the second reagent from the sample introduction unit 31 and the reagent storage unit 32 to the sample droplet generation unit 211, the first reagent droplet generation unit 212, and the second reagent droplet generation unit 213, respectively. The drive mechanism is implemented by gears, a stepping motor, a belt conveyor, and a lead screw, etc. Note that the introduction of the sample, the first reagent, and the second reagent may be performed by the user. Furthermore, the control function 41 controls the first measuring unit 22 and the second measuring unit 23.

[0033] The determination function 42 determines, for example, whether the size of the droplet measured by the first measurement unit 22 is within a specified range. The specified range is determined, for example, by the transport limit of the droplet using electrowetting or the range of droplet volume in which the measurement of the reagent is guaranteed. The specified range may also be arbitrarily entered by the user via the input interface. Furthermore, if the size of the droplet could not be measured by the first measurement unit 22, the determination function 42 may determine that the size of the droplet is not within the specified range. The determination function 42 is an example of a determination means in this embodiment.

[0034] The analysis function 43 analyzes, or calculates, the amount of target substance in the sample based on, for example, the droplet size measured by the first measuring unit 22 and the measurement results regarding the target substance by the second measuring unit 23. The amount of target substance is, for example, the concentration of the target substance in the measured droplet. The analysis function 43 is an example of the analysis means in this embodiment.

[0035] Furthermore, the analysis function 43 corrects the measurement results of the target substance by the second measurement unit 23 based on the droplet size measured by the first measurement unit 22. For example, the analysis function 43 corrects the concentration of the test substance contained in the sample droplet based on the volumes of the sample droplet and reagent droplet measured by the first measurement unit 22 and the value of the standard straight line. For example, the analysis function 43 corrects the results by multiplying the value obtained by optical measurement by Va / (Va+Vb) using the volume of the sample droplet Va and the volume of the reagent droplet Vb measured by the first measurement unit 22.

[0036] As another example, the analysis function 43 may be used to estimate the optical path length in the optical measurement by the second measurement unit 23 from the droplet size measured by the first measurement unit 22, and to analyze the amount of target substance. Alternatively, the optical path length may be corrected, for example, from a predetermined volume and optical path length stored in a memory circuit and the volume of the measured droplet.

[0037] As yet another example, the analysis function 43 may change the parameters of the measurement performed by the second measurement unit 23 based on the droplet size measured by the first measurement unit 22 and the results of the measurement of the target substance performed by the second measurement unit 23. The parameters may be, for example, light intensity, voltage, and color correction value. After changing the parameters, the analysis function 43 may instruct the second measurement unit 23 to perform the measurement of the target substance again.

[0038] Here, for example, the processing functions performed by the control function 41, judgment function 42, and analysis function 43, which are components of the processing circuit 4 shown in Figure 1, are recorded in the memory circuit in the form of a program that can be executed by a computer. The processing circuit 4 is, for example, a processor. The processor that constitutes the processing circuit 4 reads the program from the memory circuit and executes it to realize the function corresponding to the read program. In other words, the processing circuit 4 in the state where a program has been read has the functions shown in the processing circuit 4 of Figure 1.

[0039] In Figure 1, the control function 41, the determination function 42, and the analysis function 43 are shown to be realized by a single processing circuit 4, but the embodiments are not limited to this. For example, the processing circuit 4 may be composed of a combination of multiple independent processors, with each processor executing its respective program to realize these functions. Furthermore, the processing functions of the processing circuit 4 may be realized by appropriately distributing or integrating them across one or more processing circuits.

[0040] The output interface 5 is connected to the processing circuit 4 and outputs signals supplied from the processing circuit 4. The output interface 5 is implemented by, for example, a display circuit, a printing circuit, and an audio device. The display circuit includes, for example, a CRT display, a liquid crystal display, an organic EL display, an LED display, and a plasma display. The display circuit also includes a processing circuit that converts data representing the display target into a video signal and outputs the video signal to the outside. The printing circuit includes, for example, a printer. The printing circuit also includes an output circuit that outputs data representing the print target to the outside. The audio device includes, for example, a speaker. The audio device also includes an output circuit that outputs an audio signal to the outside.

[0041] Next, the specific configuration of the fluid device 2 according to this embodiment will be described. Figure 2 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analyzer 1 according to the first embodiment. In Figure 2, the sample droplet generation unit 211, the first reagent droplet generation unit 212, and the second reagent droplet generation unit 213 are represented by a single droplet generation unit 21. Also, in Figure 2, the dielectric layer 63, hydrophobic layer 64, substrate 65, electrode 66, and hydrophobic layer 67, which will be described later, are omitted.

[0042] As shown in Figure 2, the fluid device 2 includes a plurality of electrodes 62 for forming an electric field applied to the droplets. The plurality of electrodes 62 are arranged along a predetermined shape and are configured to function as the droplet generation section 21, first measurement section 22, second measurement section 23, waste liquid section 24, and cleaning liquid introduction section 25 of the fluid device 2. The relationship between the functions of these fluid devices 2 and the electrodes 62 will be described in detail below. Note that the number, arrangement, and shape of the electrodes 62 shown in Figure 2 are examples, and this embodiment is not limited thereto.

[0043] Liquid LQ containing the sample, the first reagent, or the second reagent is introduced into the holding section of the droplet generation section 21. At least a portion of the introduced liquid LQ is divided by one or more electrodes 62 near the holding section, thereby generating droplets DP. The droplets DP are moved using electrowetting, for example, in the direction indicated by the symbol D.

[0044] The first measuring unit 22 is positioned in a location corresponding to, for example, electrode 622 among the multiple electrodes 62. That is, the first measuring unit 22 measures the size of the droplet DP on electrode 622.

[0045] The second measuring unit 23 is positioned in a location corresponding to, for example, electrode 623 among the multiple electrodes 62. That is, the second measuring unit 23 performs measurements on the target substance using the droplet DP on electrode 623.

[0046] In this embodiment, the second measurement unit 23, which is an optical measurement unit, comprises a light-emitting unit 231 and a light-receiving unit 232. The light-emitting unit 231 comprises, for example, a white light source and a spectrometer. The light-emitting unit 231 emits light that has been collimated from the white light source by the spectrometer toward the droplet DP on the electrode 623. The light from the light-emitting unit 231 passes through the droplet DP along the optical path L and is received by the light-receiving unit 232. The light-receiving unit 232 detects the intensity of this light. As a result, the second measurement unit 23 measures the absorbance of the droplet DP on the electrode 623. In the example of Figure 2, the light-receiving surface of the light-receiving unit 232 is provided facing the light-emitting unit 231 in order to measure the transmitted light of the droplet DP. However, it is not limited to this, and when measuring the intensity of scattered light from the droplet DP, the light-receiving unit 232 may be provided at a predetermined angle with respect to the optical path L. The second measurement unit 23 may also measure the fluorescence intensity of the droplet DP. In this case, for example, the light-emitting unit 231 emits excitation light to irradiate the droplet, and the light-receiving unit 232 receives the resulting fluorescence.

[0047] The waste liquid section 24 is positioned to correspond to, for example, electrodes 624a and 624b among the multiple electrodes 62. That is, the waste liquid section 24 discards the droplets DP on electrodes 624a and 624b. In the example in Figure 2, droplets DP that are determined to be outside the specified size range as a result of measurement by the first measuring section 22 are moved to electrode 624a. Also, droplets that have finished being measured by the second measuring section 23 are moved to electrode 624b.

[0048] The cleaning solution introduction section 25 is positioned to correspond to, for example, electrode 625 among the multiple electrodes 62. For example, when cleaning solution is introduced to electrode 625, a portion of the introduced cleaning solution is divided by one or more electrodes 62 near electrode 625, thereby generating droplets containing the cleaning solution. In the example shown in Figure 2, electrode 625 is a reservoir electrode that holds a certain amount of cleaning solution and can dispense a portion of it by electrowetting. The cleaning solution introduction section 25 may also be provided with an inlet for injecting cleaning solution into the fluid device 2 instead of electrode 625.

[0049] Next, the cross-sectional structure of the fluid device 2 will be described. Figure 3 is a cross-sectional view showing an example of the configuration of the fluid device 2 in the analytical apparatus 1 according to the first embodiment.

[0050] As shown in Figure 3, the fluid device 2 comprises, for example, a substrate 61, an electrode 62, a dielectric layer 63, a hydrophobic layer 64, a substrate 65, an electrode 66, and a hydrophobic layer 67. A channel for the movement of liquid droplets DP is formed between the hydrophobic layer 64 and the hydrophobic layer 67.

[0051] The substrate 61 is a substrate containing materials such as glass, a printed circuit board (PCB), and silicon. The substrate 61 is located below the channel through which the droplet DP moves.

[0052] Multiple electrodes 62 are provided on the substrate 61. The material of the electrodes 62 is, for example, copper or indium tin oxide (ITO). Each electrode 62 is connected to a switch (not shown), and an independent voltage is applied to each electrode 62. When a voltage is applied to each electrode 62, an electric field for electrowetting is formed between the electrode 62 to which the voltage is applied and the portion of the electrode 66 facing that electrode 62. When this electric field is applied to a droplet DP, the wettability of the droplet DP changes. By appropriately switching the electric field applied to the droplet DP, it is possible to move the droplet DP from, for example, one electrode 62 to an adjacent electrode 62.

[0053] The dielectric layer 63 is provided on the electrode 62. The material of the dielectric layer 63 is, for example, silicon nitride (Si3N4), parylene (registered trademark), or SU-8.

[0054] The hydrophobic layer 64 is provided on top of the dielectric layer 63. Suitable materials for the hydrophobic layer 64 include, for example, polytetrafluoroethylene (PTFE) and water-repellent coating agents such as CYTOP®.

[0055] Substrate 65, like substrate 61, is a substrate containing materials such as glass, printed circuit board (PCB), and silicon. Substrate 65 is located above the channel through which the droplet DP moves. Substrate 65 may be made transparent. This facilitates observation of the droplet DP on electrode 62 and measurement by the first measurement unit 22.

[0056] Electrode 66 is provided below the substrate 65. In this embodiment, unlike electrode 62, electrode 66 is formed as a single electrode. Electrode 66 is connected to, for example, the ground potential. The material of electrode 66 is the same as electrode 62, for example, copper or indium tin oxide (ITO). When indium tin oxide is used, electrode 66 becomes a transparent electrode. This facilitates observation of the droplet DP and measurement by the first measuring unit 22. Note that electrode 66 may not be provided above at least some of the electrodes 62.

[0057] The hydrophobic layer 67 is provided beneath the electrode 66. The material of the hydrophobic layer 67 can be the same as that of the hydrophobic layer 64, for example. Furthermore, like the substrate 65, the hydrophobic layer 67 may be made transparent.

[0058] Next, with reference to Figures 4 to 7, the sample droplet generation unit 211, the first reagent droplet generation unit 212, and the second reagent droplet generation unit 213 according to this embodiment will be described.

[0059] Figure 4 is a cross-sectional view showing an example of the configuration of the sample droplet generation unit 211 in the analyzer 1 according to the first embodiment. As shown in Figure 4, in the sample droplet generation unit 211, the substrate 65 is provided with an opening for introducing a sample S. Figure 4 also shows the probe 31a of the sample introduction unit 31. The probe 31a is a sampling probe capable of, for example, aspirating a sample S from a sample container and discharging the sample S into the holding unit 211a of the sample droplet generation unit 211. At least a portion of the sample S introduced into the holding unit 211a is divided into sample droplets SDP by an electrode 62 near the holding unit 211a and moved. In the example of Figure 4, a hydrophobic layer 67 is provided on the side surface of the opening of the substrate 65. Note that the hydrophobic layer 67 on the side surface of the opening of the substrate 65 may be omitted.

[0060] A reservoir electrode may be provided in the sample droplet generation unit 211. Figure 5 is a cross-sectional view showing another configuration example of the sample droplet generation unit 211 in the analyzer 1 according to the first embodiment. As shown in Figure 5, the sample droplet generation unit 211 is provided with an electrode 621 as a reservoir electrode. In this case, at least a portion of the introduced sample S is divided and moved into sample droplets SDP by the electrode 621 and other electrodes 62 near the electrode 621.

[0061] Figure 6 is a cross-sectional view showing an example of the configuration of the first reagent droplet generation unit 212 in the analyzer 1 according to the first embodiment. As shown in Figure 6, in the first reagent droplet generation unit 212, the substrate 65 is provided with an opening for introducing the first reagent R1. Figure 6 also shows a first reagent bottle 32a that contains the first reagent R1. The first reagent bottle 32a is provided with a dispensing unit 32b for dispensing the first reagent R1 from, for example, the holding unit 212a of the first reagent droplet generation unit 212. The movement of the first reagent bottle 32a is performed, for example, by driving the arm of the reagent storage unit 32 with a drive mechanism. The dispensing of the first reagent R1 from the dispensing unit 32b is performed, for example, by a pump provided in the drive mechanism. At least a portion of the introduced first reagent R1 is divided into first reagent droplets RDP1 by the electrode 62 near the holding unit 212a and moved.

[0062] Figure 7 is a cross-sectional view showing an example of the configuration of the second reagent droplet generation unit 213 in the analyzer 1 according to the first embodiment. The configuration of the second reagent droplet generation unit 213 is the same as the configuration of the first reagent droplet generation unit 212 described above. That is, as shown in Figure 7, in the second reagent droplet generation unit 213, the substrate 65 is provided with an opening for introducing the second reagent R2. Figure 7 also shows a second reagent bottle 32c that contains the second reagent R2. The second reagent bottle 32c is provided with a dispensing unit 32d for dispensing the second reagent R2 from the holding unit 213a of the second reagent droplet generation unit 213. The movement of the second reagent bottle 32c is performed, for example, by driving the arm of the reagent storage unit 32 with a drive mechanism. The dispensing of the second reagent R2 from the dispensing unit 32d is performed, for example, by a pump provided in the drive mechanism. At least a portion of the introduced second reagent R2 is divided into second reagent droplets RDP2 by the electrode 62 near the holding unit 213a and moved.

[0063] In this way, by introducing the sample S, the first reagent R1, and the second reagent R2 without direct contact with the fluid device 2, cleaning of the fluid device 2 can be facilitated. Furthermore, contamination in the sample droplet generation section 211, the first reagent droplet generation section 212, and the second reagent droplet generation section 213 can be suppressed.

[0064] In the example described above, sample S was introduced using a sampling probe, and the first reagent R1 and the second reagent R2 were introduced using a reagent bottle equipped with a dispensing nozzle. However, the method is not limited to this; sample S may also be introduced using a sample container equipped with a dispensing nozzle, or the first reagent R1 and the second reagent R2 may be introduced using a sampling probe.

[0065] Next, an example of the implementation of the second measuring unit 23 according to this embodiment will be described. Figure 8 is a cross-sectional view showing an example of the configuration of the second measuring unit 23 in the analytical apparatus according to the first embodiment.

[0066] As shown in Figure 8, the light-emitting unit 231 of the second measuring unit 23 is provided, for example, below the substrate 61. The light-receiving unit 232 of the second measuring unit 23 is provided, for example, on top of the substrate 65. In this case, optical measurement is performed on the droplet DP on the electrode 623 using a vertical optical path L.

[0067] In the example shown in Figure 8, at least the portions of the substrate 61, dielectric layer 63, hydrophobic layer 64, substrate 65, and hydrophobic layer 67 located along the optical path L are made transparent. Furthermore, an aperture 623a is provided on electrode 623 along the optical path L, and an aperture 66a is provided on electrode 66 along the optical path L. By providing apertures 623a and 66a, the influence of electrodes 623 and 66 on optical measurements can be suppressed.

[0068] Furthermore, in the example shown in Figure 8, the light-emitting unit 231 is provided below the substrate 61, and the light-receiving unit 232 is provided on top of the substrate 65. However, the system is not limited to this configuration; the light-receiving unit 232 may be provided below the substrate 61, and the light-emitting unit 231 may be provided on top of the substrate 65. Also, the direction of optical measurement is not limited to the vertical direction, but may be any direction, such as the horizontal direction.

[0069] Furthermore, as shown in Figure 9, if electrodes 623 and 66 are made of light-transmitting material, the apertures 623a and 66a on the optical path L do not need to be provided. Figure 9 is a cross-sectional view showing another implementation example of the second measuring unit 23 in the analytical apparatus 1 according to the first embodiment. In this case, for example, the processing of electrodes 623 and 66 can be made easier.

[0070] Next, an example of operation of the analyzer 1 according to the first embodiment, configured as described above, will be explained with reference to Figures 10 to 12. Figure 10 is a flowchart showing an example of operation of the analyzer 1 according to the first embodiment. Figures 11 and 12 are schematic plan views showing an example of operation of the analyzer 1 according to the first embodiment. This example of operation is performed, for example, when a user uses the analyzer 1 to perform an analysis of a target substance contained in a sample S. In the following explanation, unless otherwise specified, the sample droplet SDP, the first reagent droplet RDP1, and the second reagent droplet RDP2 will all be referred to as droplets DP.

[0071] First, as shown in Figure 10, droplets DP are generated (step S11). More specifically, the control function 41 of the processing circuit 4 causes the droplet generation unit 21 to generate droplets DP. For example, when generating sample droplets SDP, the control function 41 first controls the drive mechanism to introduce the sample S into the sample droplet generation unit 211 using the probe 31a of the sample introduction unit 31. Then, the control function 41 generates sample droplets SDP by controlling the voltage applied to the electrode 62 near the sample droplet generation unit 211. On the other hand, when generating the first reagent droplet RDP1 and the second reagent droplet RDP2, the control function 41 first controls the drive mechanism to introduce the first reagent droplet RDP1 and the second reagent droplet RDP2 from the first reagent bottle 32a and the second reagent bottle 32c into the first reagent droplet generation unit 212 and the second reagent droplet generation unit 213, respectively. Subsequently, the control function 41 generates the first reagent droplet RDP1 and the second reagent droplet RDP2, respectively, by controlling the voltage applied to the electrodes 62 near the first reagent droplet generation unit 212 and the second reagent droplet generation unit 213.

[0072] Next, the size of the droplet DP is measured (step S13). More specifically, as shown in Figure 11, the control function 41 of the processing circuit 4 moves the droplet DP onto the electrode 622 by controlling the voltage applied to the electrode 62. Subsequently, the control function 41 measures the size of the droplet DP by controlling the first measuring unit 22.

[0073] Next, as shown in Figure 10, it is determined whether the droplet size is within a specified range (step S15). More specifically, the determination function 42 of the processing circuit 4 determines whether the droplet size DP measured by the first measurement unit 22 is within a specified range.

[0074] If the size of the droplet DP is determined to be within the specified range (step S15: YES), measurements concerning the target substance are performed (step S17). More specifically, as shown in Figure 11, the control function 41 of the processing circuit 4 moves the droplet DP onto the electrode 623 by controlling the voltage applied to the electrode 62. Subsequently, the control function 41 controls the second measurement unit 23 to perform measurements concerning the target substance using the droplet DP.

[0075] On the other hand, as shown in Figure 10, if it is determined that the size of the droplet DP is not within the specified range (step S15: NO), the droplet is discarded (step S19). More specifically, as shown in Figure 12, the control function 41 of the processing circuit 4 moves the droplet DP onto the electrode 624a by controlling the voltage applied to the electrode 62. The example in Figure 12 shows the case where the size of the droplet DP is smaller than the specified range. The same applies when the size of the droplet DP is larger than the specified range. After step S19, the process returns to step S11 and a droplet is generated again.

[0076] After step S17, the measurement results regarding the target substance are analyzed (step S21). More specifically, the analysis function 43 of the processing circuit 4 analyzes the amount of target substance in the sample S based on, for example, the size of the droplet DP measured by the first measurement unit 22 and the measurement results regarding the target substance measured by the second measurement unit 23.

[0077] Next, the measured values ​​are output (step S23). More specifically, the analysis function 43 of the processing circuit 4 outputs, for example, the amount of the target substance in the analyzed sample S to the output interface 5. The output interface 5 displays, for example, the amount of the target substance.

[0078] Next, the main body of the device is cleaned (step S25). More specifically, the control function 41 of the processing circuit 4 introduces cleaning fluid into the fluid device 2 from the cleaning fluid introduction section 25. Subsequently, the control function 41 generates droplets containing cleaning fluid by controlling the voltage applied to the electrode 62 and moves these droplets within the fluid device 2.

[0079] The operation of the analytical apparatus 1 according to this embodiment is completed by the above steps.

[0080] As described above, according to the analytical apparatus 1 of the first embodiment, the amount of target substance in the sample S can be analyzed based on the size of the droplet DP measured by the first measuring unit 22 and the results of the measurement of the target substance performed by the second measuring unit 23. This reduces the influence of the size of the generated droplet DP on the measurement results of the target substance. Therefore, the accuracy of the analysis results in the analytical apparatus 1 can be improved.

[0081] Furthermore, by correcting the results of the target substance measurement performed by the second measurement unit 23 based on the size of the droplet DP measured by the first measurement unit 22, it is possible to reduce the variation in the measurement results of the target substance due to variations in the size of the generated droplet DP.

[0082] Furthermore, if the measured droplet size DP is determined to be outside the specified range, the droplet DP can be discarded, thus avoiding measurement of droplets outside the specified range. This improves the throughput of the analyzer 1. In addition, when mixing and reacting the sample droplet SDP with the reagent droplet, the waste of reagents is avoided, thereby reducing the cost of the test.

[0083] (Modification 1 of the first embodiment) In the first embodiment described above, the first measurement unit 22 included an image acquisition unit for acquiring an image of the droplet DP. In the modified example 1 of the first embodiment described below, the first measurement unit 22 includes an impedance acquisition unit for acquiring the impedance of the droplet DP. The modified example 1 of the first embodiment will now be described, focusing on the differences from the first embodiment.

[0084] Figure 13 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analyzer 1 according to Modification 1 of the First Embodiment. As shown in Figure 13, the first measuring unit 22 according to this modification includes an impedance sensor 221 as an impedance acquisition unit. The first measuring unit 22 also includes, for example, wiring 222 that is electrically connected to the impedance sensor 221 and contacts the droplet DP on the electrode 622. The first measuring unit 22 measures the impedance Z1 of the droplet DP on the electrode 622 using the impedance sensor 221 and the wiring 222. The impedance Z1 is the capacitance of the droplet DP, etc. The first measuring unit 22 may also calculate the volume of the droplet DP using the impedance Z1 of the droplet DP.

[0085] This modified version allows for an increased number of methods for measuring the size of the droplet DP. The impedance acquisition unit may be used in conjunction with the image acquisition unit described above.

[0086] (Modification 2 of the first embodiment) In the first embodiment described above, the second measuring unit 23 performed optical measurements. In the modified example 2 of the first embodiment described below, the second measuring unit 23 performs electrochemical measurements. The modified example 2 of the first embodiment will be described below, focusing on the differences from the first embodiment.

[0087] Figure 14 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analyzer 1 according to a modified example 2 of the first embodiment. As shown in Figure 14, the second measuring unit 23 according to this modified example includes, for example, an impedance sensor 233 for acquiring impedance and wiring 234 that is electrically connected to the impedance sensor 233 and in contact with the droplet DP on the electrode 623. The second measuring unit 23 acquires the impedance Z2 of the droplet DP on the electrode 623 using the impedance sensor 233 and the wiring 234. Then, the second measuring unit 23 calculates, for example, the concentration of the target substance contained in the droplet DP using the impedance Z2 of the droplet DP.

[0088] This modified version allows for an increase in the methods for measuring target substances using droplets DP. The second measurement unit 23 may measure the potential difference generated in the droplet DP instead of the impedance Z2 of the droplet DP.

[0089] (Modification 3 of the first embodiment) Next, a modification 3 of the first embodiment, in which the second measuring unit 23 performs hue measurement, will be described. Figure 15 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analyzer 1 according to modification 3 of the first embodiment.

[0090] As shown in Figure 15, the second measurement unit 23 in this modified example is equipped with an image sensor for measuring hue. The second measurement unit 23 measures the hue of the droplet DP at the electrode 623.

[0091] This modified version allows for an increase in the methods for measuring target substances using droplet DP. The second measurement unit 23 may also measure the intensity of bioluminescence or chemiluminescence of the droplet DP using an image sensor.

[0092] (Modification 4 of the first embodiment) Next, a modification 4 of the first embodiment described above will be explained, in which the second measuring unit 23 has a structure that increases the optical path length. Figure 16 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analytical apparatus 1 according to modification 4 of the first embodiment.

[0093] As shown in Figure 16, the distance between the light-emitting unit 231 and the light-receiving unit 232 in the second measuring unit 23 according to this modified example is greater than the distance between the light-emitting unit 231 and the light-receiving unit 232 in the second measuring unit 23 according to the first embodiment. In addition, in this modified example, the electrode 623 has a horizontally elongated shape. The droplet DP located on the electrode 623 is stretched horizontally by the shape of the electrode 623. As a result, the optical path L of light from the light-emitting unit 231 to the light-receiving unit 232 becomes longer.

[0094] According to this modified version, when it is necessary to increase the optical path length, such as when measuring the transmitted light of a droplet DP, measurements regarding the target material can be performed more appropriately.

[0095] (Modification 5 of the first embodiment) In the first embodiment described above, if it was determined that the size of the droplet DP was outside the specified range, the droplet DP was discarded. In Modification 5 of the first embodiment, described below, a function is provided to replenish or divide the droplet DP if it is determined that the size of the droplet DP is outside the specified range. The following description of this modification will focus on the differences from the first embodiment.

[0096] In this modified example, if the size of the droplet DP is determined to be smaller than a specified range, the droplet generation unit 21 further generates a supplementary droplet DPR to replenish the droplet DP. The supplementary droplet DPR is generated by the droplet generation unit 21, for example, in the same manner as the droplet DP.

[0097] Furthermore, in this modified version, if it is determined that the size of the droplet DP is larger than a specified range, a dividing section is further provided that divides the droplet DP into multiple droplets smaller in size than the droplet DP by applying an electric field. The dividing section is composed of, for example, an electrode 622 and an electrode 62 adjacent to electrode 622.

[0098] Figure 17 is a flowchart showing an example of operation of the analyzer 1 according to modification 5 of the first embodiment. As shown in Figure 17, after step S13, it is determined whether the size of the droplet DP is smaller than the specified range (step S15a). More specifically, the determination function 42 of the processing circuit 4 determines whether the size of the droplet DP measured by the first measurement unit 22 is smaller than the specified range.

[0099] If it is determined that the size of the droplet DP is smaller than the specified range (step S15a: YES), a replenishment droplet DPR is generated (step S151). More specifically, as shown in Figure 18, if it is determined that the size of the droplet DP on the electrode 622 located in the first measurement unit 22 is smaller than the specified range, as shown in Figure 19, the control function 41 of the processing circuit 4 causes the droplet generation unit 21 to generate a replenishment droplet DPR to replenish the droplet DP.

[0100] As shown in Figure 17, after step S151, the replenishment droplet DPR is fused (step S153). More specifically, the control function 41 of the processing circuit 4 controls the voltage applied to electrode 62 to move the replenishment droplet DPR to electrode 622 and fuse it with droplet DP. After step S153, steps S17 onward are performed as in the first embodiment. That is, measurements regarding the target substance are performed using the droplet formed by the fusion of the replenishment droplet DPR and droplet DP. The droplet formed by the fusion of the replenishment droplet DPR and droplet DP may be discarded. In this case, the replenishment droplet DPR may contain a washing solution.

[0101] On the other hand, if in step S15a it is not determined that the size of the droplet DP is smaller than the specified range (step S15a: NO), then it is determined whether or not the size of the droplet DP is larger than the specified range (step S15b). More specifically, the determination function 42 of the processing circuit 4 determines whether or not the size of the droplet DP measured by the first measurement unit 22 is larger than the specified range.

[0102] If it is determined that the size of droplet DP is larger than the specified range (step S15b: YES), droplet DP is divided (step S155). More specifically, as shown in Figure 20, if it is determined that the size of droplet DP is larger than the specified range, the control function 41 of the processing circuit 4 controls the voltage applied to electrode 62 to stretch droplet DP onto multiple electrodes 62. More specifically, the control function 41 applies voltage to electrode 622 and electrodes 62a and 62b adjacent to electrode 622 to stretch droplet DP onto electrode 622, electrode 62a and electrode 62b. Then, as shown in Figure 21, the control function 41 keeps the voltage applied to electrodes 62a and 62b, but removes the voltage from electrode 622. As a result, droplet DP is divided into multiple droplets DP1 and DP2, which are smaller in size than droplet DP. Electrodes 622, 62a, and 62b are examples of the divided parts in this modified example. That is, electrodes 622, 62a, and 62b divide the droplet DP into multiple droplets smaller in size than the droplet DP by applying an electric field.

[0103] As shown in Figure 17, after step S155, some of the droplets are discarded (step S157). More specifically, as shown in Figure 21, the control function 41 of the processing circuit 4 controls, for example, the voltage applied to electrode 62 to move droplet DP2 on electrode 62b to electrode 624 where the waste liquid unit 24 is located. After step S157, steps S17 onward are carried out in the same manner as in the first embodiment. More specifically, the control function 41 controls, for example, the voltage applied to electrode 62 to move droplet DP1 on electrode 62a to electrode 623 where the second measuring unit 23 is located. After that, measurements regarding the target substance are performed using droplet DP1. Note that both droplet DP1 and droplet DP2 may be discarded.

[0104] According to this modified version, droplets DP whose size falls outside the specified range can also be used for measurement by the second measuring unit 23. Therefore, the amount of waste sample S can be reduced.

[0105] Furthermore, in DMF devices in general, during the generation and movement of droplets (DP), some of the droplets may remain behind, or droplets may unintentionally fuse with other droplets. If some of the droplets remain behind, the remaining portion may be too large to be moved using electrowetting. Similarly, droplets that have unintentionally fused may also be too large to be moved using electrowetting. According to this modification, in such cases, the remaining portion of the droplets or the fused droplets can be moved.

[0106] The above description assumes that the analyzer 1 has both the function of generating replenishment droplets (DPR) and the function of splitting droplets (DP). However, it is not limited to this, and the analyzer 1 may have either the function of generating replenishment droplets (DPR) or the function of splitting droplets (DP).

[0107] Furthermore, the generation of replenishment droplets (DPRs) and the division of droplets (DPs) may be combined with a determination of whether or not they fall within a specified range. For example, a first range and a second range different from the first range may be defined as the specified range. Then, if the size of droplet DP is smaller than the first range and within the second range, a replenishment droplet (DPR) may be generated; if the size of droplet DP is larger than the first range and within the second range, droplet DP may be divided; and if the size of droplet DP is not within the second range, droplet DP may be discarded.

[0108] (Second Embodiment) Next, a second embodiment will be described in which the analyzer 1 according to the first embodiment is provided with a region for mixing, stirring, and reacting droplets DP. Figure 22 is a block diagram showing an example of the configuration of the analyzer 1 according to the second embodiment. The following description will focus on the differences from the first embodiment.

[0109] As shown in Figure 22, the fluid device 2 of this embodiment further comprises a mixing and stirring section 26 and a reaction section 27. Both the mixing and stirring section 26 and the reaction section 27 are regions formed by one or more electrodes 62.

[0110] The mixing and stirring unit 26 mixes and stirs multiple droplets DP using electrowetting. For example, the mixing and stirring unit 26 mixes and stirs the sample droplet SDP generated by the sample droplet generation unit 211 with the first reagent droplet RDP1 generated by the first reagent droplet generation unit 212. The mixing and stirring unit 26 also mixes and stirs the mixed droplet, which is a mixture of the sample droplet SDP and the first reagent droplet RDP1, with the second reagent droplet RDP2 generated by the second reagent droplet generation unit 213.

[0111] The reaction unit 27 reacts a mixed droplet of sample droplet SDP and reagent droplet. For example, the reaction unit 27 holds the mixed droplet and allows a chemical reaction to occur within it. The chemical reaction is, for example, the reaction between sample S and first reagent R1 within a mixed droplet containing a mixture of sample droplet SDP and first reagent droplet RDP1.

[0112] Next, the specific configuration of the fluid device 2 according to this embodiment will be described. Figure 23 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analyzer 1 according to the second embodiment.

[0113] As shown in Figure 23, in this embodiment, the droplet generation unit 21 is provided with a sample droplet generation unit 211, a first reagent droplet generation unit 212, and a second reagent droplet generation unit 213. The first measurement unit 22 is provided with a first measurement unit 22a for measuring the size of the sample droplet SDP, a first measurement unit 22b for measuring the size of the first reagent droplet RDP1, and a first measurement unit 22c for measuring the size of the second reagent droplet RDP2. The first measurement units 22a, 22b, and 22c are arranged to correspond to electrodes 622a, 622b, and 622c, respectively, among the plurality of electrodes 62.

[0114] The mixing and stirring unit 26 is positioned in accordance with electrode 626 among a plurality of electrodes 62. The droplet DP whose size has been measured by the first measuring unit 22 is moved to electrode 626 and mixed and stirred. In the example in Figure 23, multiple electrodes 626 are provided. When mixing droplets, for example, two droplets DP are moved onto adjacent electrodes 626, and then the application of voltage to one of the electrodes 626 is stopped. When stirring droplets, the mixed droplet is moved on the electrode 626. For example, the mixed droplet is moved back and forth between adjacent electrodes 626, or the mixed droplet is rotated within a 2x2 arrangement of electrodes 626.

[0115] The reaction section 27 is positioned in accordance with electrode 627 among the multiple electrodes 62. The mixed droplet, mixed and stirred by the mixing and stirring section 26, is moved to electrode 627 and held there for a certain period of time required for the reaction. This allows the chemical reaction within the mixed droplet to proceed. Only one electrode 627 is required. However, in the example shown in Figure 23, multiple electrodes 627 are provided. This allows, for example, the reaction of multiple mixed droplets to proceed simultaneously.

[0116] The mixed droplets that have undergone a chemical reaction in the reaction unit 27 are moved to the electrode 623 and measured by the second measurement unit 23. It may also be possible to return the droplets to the reaction unit 27 after measurement by the second measurement unit 23.

[0117] Furthermore, at least some of the electrodes 62 in the mixing and stirring section 26 and the reaction section 27 may overlap. For example, the reaction section 27 may be provided in the same area as the mixing and stirring section 26. In this case, the step of moving the stirred mixed droplets to the reaction section 27 can be omitted. Alternatively, the second measuring section 23 may be provided in the same area as at least one of the reaction sections 27. In this case, the step of moving the mixed droplets that have undergone the chemical reaction to the second measuring section 23 can be omitted.

[0118] Next, with reference to Figure 24, an example of operation of the analyzer 1 according to the second embodiment, configured as described above, will be explained. Figure 24 is a flowchart showing an example of operation of the analyzer according to the second embodiment. In the following explanation, unless otherwise specified, the sample droplet SDP, the first reagent droplet RDP1, the second reagent droplet RDP2, and the mixed droplet will all be referred to as droplet DP.

[0119] In this embodiment, in step S11, a sample droplet SDP, a first reagent droplet RDP1, and a second reagent droplet RDP2 are generated. Next, in step S13, the sizes of the generated sample droplet SDP, the first reagent droplet RDP1, and the second reagent droplet RDP2 are measured. Next, in step S15, it is determined whether the sizes of the sample droplet SDP, the first reagent droplet RDP1, and the second reagent droplet RDP2 are within a specified range. If it is determined that the size is not within the specified range (step S15: NO), the sample droplet SDP, the first reagent droplet RDP1, and the second reagent droplet RDP2 are moved by the electrode 624a shown in Figure 23 and discarded by the waste liquid unit 24. After that, droplets are generated again (step S11). In this embodiment, if the size of a droplet is determined to be within the specified range, the generation of droplets again may be omitted.

[0120] On the other hand, if it is determined that the size is within the specified range (step S15: NO), the droplet DP is mixed and stirred (step S27). More specifically, the control function 41 of the processing circuit 4 controls the voltage applied to the electrode 62 to move, for example, the sample droplet SDP and the first reagent droplet RDP1 onto different electrodes 626, respectively. Then, the control function 41 controls the voltage applied to the electrode 62 to mix the sample droplet SDP and the first reagent droplet RDP1 into a single mixed droplet. Then, the control function 41 controls the voltage applied to the electrode 62 to stir the mixed droplet. Then, in the same manner, this mixed droplet is mixed with the second reagent droplet RDP2 and stirred.

[0121] Next, the droplet DP is reacted (step S29). More specifically, the control function 41 of the processing circuit 4 controls the voltage applied to the electrode 62, thereby moving the mixed droplet of the sample droplet SDP, the first reagent droplet RDP, and the second reagent droplet RDP2 onto the electrode 627. The control function 41 then holds this mixed droplet on the electrode 627 for the time required for the reaction. After that, measurements concerning the target substance are performed using this mixed droplet (step S17).

[0122] The subsequent steps are the same as in the first embodiment.

[0123] According to this embodiment, a region for mixing and stirring the droplets DP is secured, making mixing and stirring easier. Furthermore, a region for reacting the mixed droplets is secured, allowing sufficient time for chemical reactions within the mixed droplets.

[0124] (Third embodiment) In the second embodiment described above, after measuring the size of the droplet DP, the sample droplet SDP, the first reagent droplet RDP1, and the second reagent droplet RDP2 are moved to the same electrode 624a and discarded by the waste liquid section 24. In this case, contamination may occur because the flow path of the discarded droplets intersects with the flow path of the droplets moved to the second measurement section 23. This will be explained with reference to Figure 25. Figure 25 is a schematic diagram illustrating contamination in the analyzer 1 according to the second embodiment.

[0125] Figure 25 shows, as an example, a case where the size of the sample droplet SDP is outside the specified range, while the size of the first reagent droplet RDP1 is within the specified range. In this case, the sample droplet SDP moves from electrode 622a to electrode 642a along channel D1. Meanwhile, the first reagent droplet RDP1 moves from electrode 622b to the mixing and stirring section 26, reaction section 27, and second measurement section 23 along channel D2. Here, channels D1 and D2 intersect in region A. In this case, there is a risk that the first reagent droplet RDP1 may be contaminated if a portion of the sample droplet SDP, which is scheduled for disposal, remains in region A.

[0126] Therefore, the third embodiment described below is configured such that the flow path for discarded droplets DP and the flow path for droplets DP moved to the second measuring unit 23 do not intersect. Figure 26 is a block diagram showing an example configuration of the analyzer 1 according to the third embodiment. The following description will focus on the differences between this embodiment and the second embodiment.

[0127] As shown in Figure 26, in this embodiment, if the size of the droplet DP measured by the first measuring unit 22 is determined to be outside the specified range, a flow path is provided for sending the droplet DP to the waste liquid section 24 without passing through the flow path to the second measuring unit 23. For example, the flow path through which the sample droplet SDP, whose size has been measured by the first measuring unit 22, is moved to the waste liquid section 24 does not intersect with the flow path through which the first reagent droplet RDP1 and the second reagent droplet RDP2 are moved to the mixing and stirring unit 26. Similarly, the flow path through which the first reagent droplet RDP1, whose size has been measured by the first measuring unit, is headed towards the waste liquid section 24 does not intersect with the flow path through which the sample droplet SDP and the second reagent droplet RDP2 are moved to the mixing and stirring unit 26. Furthermore, the flow path through which the second reagent droplet RDP2, whose size has been measured by the first measuring unit, is headed towards the waste liquid section 24 does not intersect with the flow path through which the sample droplet SDP and the first reagent droplet RDP1 are moved to the mixing and stirring unit 26.

[0128] The specific configuration of such a flow path will be described below with reference to Figure 27. Figure 27 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analytical apparatus 1 according to the third embodiment.

[0129] As shown in Figure 27, the fluid device 2 according to this embodiment is equipped with different waste liquid section electrodes 24 for the sample droplet SDP, the first reagent droplet RDP1, and the second reagent droplet RDP2. That is, if it is determined that the size of each is outside the specified range, the sample droplet SDP is moved to electrode 624a1, the first reagent droplet RDP1 is moved to electrode 624a2, and the second reagent droplet RDP2 is moved to electrode 624a3. For example, the sample droplet SDP that is determined to be outside the specified range is moved to electrode 626 along the first channel F1. On the other hand, the sample droplet SDP that is determined to be outside the specified range is moved to electrode 624a1 along the second channel F2. The waste liquid section 24 discards the droplets DP on electrodes 624a1, 624a2, and 624a3.

[0130] Thus, in this embodiment, the multiple electrodes 62 in the fluid device 2 are provided with a first flow path F1 and a second flow path F2. The first flow path F1 is a flow path that moves the droplet DP measured by the first measuring unit 22 to be measured by the second measuring unit 23. The second flow path F2 is a flow path different from the first flow path F1 and is a flow path that moves the droplet DP measured by the first measuring unit 22 to the waste liquid unit 24.

[0131] As described above, according to this embodiment, the occurrence of contamination in the fluid device 2 can be suppressed.

[0132] (Fourth Embodiment) Next, a fourth embodiment will be described, which includes a function to heat the droplet DP in the fluid device 2. Figure 28 is a block diagram showing an example configuration of the analyzer 1 according to the fourth embodiment. The following description will focus on the differences from the third embodiment.

[0133] As shown in Figure 28, the fluid device 2 according to this embodiment further includes a heating unit 28. The heating unit 28 heats the droplets DP within the fluid device 2. The heating unit 28 is, for example, a heating wire provided below the electrodes 62. In this embodiment, the heating unit 28 is provided in the mixing and stirring unit 26, the reaction unit 27, and the second measuring unit 23, and heats the droplets DP located on these electrodes 62. The temperature at which the droplets DP are heated is, for example, 37°C.

[0134] The specific configuration of the heating unit 28 will now be described with reference to Figure 29. Figure 29 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analytical apparatus 1 according to the fourth embodiment. In the example in Figure 29, the heating unit 28 is located below the electrode 62 where the mixing and stirring unit 26, the reaction unit 27, and the second measuring unit 23 are located.

[0135] The heating unit 28 may be provided in at least one of the mixing and stirring unit 26, the reaction unit 27, and the second measuring unit 23. The heating unit 28 may also uniformly heat the reaction unit 27 and the second measuring unit 23. This allows the second measuring unit 23 to perform measurements on the target substance under the same temperature conditions as the reaction unit 27. Furthermore, the heating unit 28 may also be provided in the first measuring unit 22.

[0136] According to this embodiment, by heating the droplet DP with the heating unit 28, for example, the reaction within the mixed droplet can be promoted.

[0137] (Fifth embodiment) A fifth embodiment will be described in which the first measuring unit 22 is configured to monitor the flow path uniformity of the fluid device 2, as described in the fourth embodiment above. Figure 30 is a block diagram showing an example of the configuration of the analytical apparatus 1 according to the fifth embodiment.

[0138] As shown in Figure 30, in this embodiment, the first measuring unit 22 measures the size of droplets DP immediately after they are generated by the droplet generation unit 21, as well as the size of droplets DP located in, for example, the mixing and stirring unit 26, the reaction unit 27, and the second measuring unit 23.

[0139] The specific configuration of the first measuring unit 22 according to this embodiment will be described below with reference to Figure 31. Figure 31 is a schematic plan view showing an example of the configuration of the fluid device 2 in the analytical apparatus 1 according to the fifth embodiment.

[0140] As shown in Figure 31, the first measuring unit 22 is, for example, an image acquisition unit that acquires an image of a droplet DP. In this embodiment, the first measuring unit 22 acquires an image of a droplet DP located in the region within the dashed-dotted line in Figure 31. This region includes, for example, the mixing and stirring unit 26, the reaction unit 27, and the second measuring unit 23, and the flow path between them. Based on the acquired image, the first measuring unit 22 measures at least one of the following: movement of the droplet DP, mixing, stirring, and reaction. For example, the first measuring unit 22 measures the size of the droplet DP in the region over time. Alternatively, the first measuring unit 22 measures the size of the droplet DP each time it moves between the electrodes 62. The first measuring unit 22 also measures the size of a mixed droplet being mixed and stirred on electrode 626. The first measuring unit 22 also measures the size of a mixed droplet undergoing a reaction on electrode 627. The first measuring unit 22 also measures the size of a mixed droplet undergoing measurement related to a target substance on electrode 623. In this embodiment, the determination function 42 of the processing circuit 4 may, for example, determine whether the size of the droplet DP is within a specified range each time the droplet DP moves between the electrodes 62. Also, the area monitored by the first measurement unit 22 is not limited to the example in Figure 31, but can be arbitrary.

[0141] As described above, according to this embodiment, the accuracy of measurements regarding the target substance can be improved by having the first measuring unit 22 monitor the flow path uniformity of the fluid device 2. For example, by measuring the size of the droplet DP on the second measuring unit 23, it is possible to respond even if the size of the droplet DP changes while it is being moved to the second measuring unit 23.

[0142] Furthermore, in this embodiment, as in Modification 5 of the First Embodiment described above, a function may be provided to replenish or divide the droplet DP if it is determined that the size of the droplet DP is outside the specified range. This allows for handling cases such as when a portion of the droplet DP remains behind or when droplets DP unintentionally fuse with other droplets during movement of the droplet DP in the mixing and stirring section 26 or the reaction section 27.

[0143] (Sixth Embodiment) Next, a sixth embodiment will be described, which includes a function to stop the inspection in the event of a problem, as in the fifth embodiment. Figure 32 is a block diagram showing an example configuration of the analytical apparatus 1 according to the sixth embodiment. The following description will focus on the differences between this embodiment and the fifth embodiment.

[0144] As shown in Figure 32, the processing circuit 4 of this embodiment further includes a cancellation function 44. The cancellation function 44 cancels the inspection by the analyzer 1 based on, for example, the properties of the sample S, contamination of the analyzer 1, a malfunction of the first measuring unit 22, and a malfunction of the second measuring unit 23. The cancellation function 44 is an example of a cancellation means in this embodiment.

[0145] The properties of sample S refer to whether or not it is determined that it is impossible to generate sample droplets SP within a specified size range using sample S. For example, if the sample droplet generation unit 211 fails to generate sample droplets SP within a specified size range after repeating the generation of sample droplets SP a specified number of times, the termination function 44 determines that it is impossible to generate sample droplets SP within a specified size range and terminates the inspection by the analyzer 1 based on the properties of sample S. The specified number of times is stored in a memory circuit beforehand, for example. The specified number of times may also be set by the user. The termination function 44 may also terminate the inspection by the analyzer 1 based on the properties of the first reagent R1 and the second reagent R2 in a similar manner.

[0146] Contamination of the analyzer 1 means, for example, that a portion of the droplet DP remains in the flow path of the fluid device 2. For example, the abort function 44 determines whether a portion of the droplet DP remains on the electrode 62 based on the image acquired by the first measuring unit 22. If it is determined that a portion of the droplet DP remains, the abort function 44 aborts the inspection by the analyzer 1 based on the contamination of the analyzer 1.

[0147] A malfunction in the first measurement unit 22 and the second measurement unit 23 means, for example, when the first measurement unit 22 and the second measurement unit 23 are made to perform control measurements and it is determined that there is a problem with the result of at least one of the measurements. The control measurements are performed, for example, using a standard sample. For example, if the size of the sample droplet SDP containing the standard sample is not within the specified range, or if the result of the measurement of the target substance performed using the sample droplet SDP containing the standard sample is not within the specified range, the stop function 44 will stop the inspection by the analyzer 1 based on the malfunction of the first measurement unit 22 and the second measurement unit 23.

[0148] Next, with reference to Figure 33, an example of operation of the analytical apparatus 1 according to the sixth embodiment, configured as described above, will be explained. Figure 33 is a flowchart showing an example of operation of the analytical apparatus 1 according to the sixth embodiment.

[0149] As shown in Figure 33, first, it is determined whether the flow path, the first measurement unit, and the second measurement unit are all functioning normally (step S31). For example, the stop function 44 of the processing circuit 4 controls the first measurement unit 22 to acquire an image of the flow path of the fluid device 2. Then, based on the acquired image, it is determined whether a portion of the droplet DP remains. After that, the stop function 44 causes the first measurement unit 22 to perform a control measurement and determines if there is a malfunction in the first measurement unit 22. After that, the stop function 44 causes the second measurement unit 23 to perform a control measurement and determines if there is a malfunction in the second measurement unit 23.

[0150] If the flow path, the first measurement unit, and the second measurement unit are all determined to be normal (step S31: YES), then 0 is assigned to k (step S33). More specifically, the termination function 44 of the processing circuit 4 prepares k as an internal parameter, assigns 0 to k, and stores it in the memory circuit. Note that k represents the number of trials in which the sample droplet SDP was generated.

[0151] On the other hand, if the flow path, the first measurement unit, and the second measurement unit are not determined to be normal (step S31: NO), that is, if at least one of the flow path, the first measurement unit, and the second measurement unit is determined to be abnormal, the test is terminated (step S35). More specifically, the termination function 44 of the processing circuit 4 causes an error display to be output to the output interface 5.

[0152] After step S33, steps S11 to S15 described above are performed. Also, if it is determined in step S15 that the droplet size is within the specified range (step S15: YES), steps S27 to S25 described above are performed. On the other hand, if it is determined in step S15 that the droplet size is not within the specified range (step S15: NO), step S19 described above is performed.

[0153] After step S19, k is increased by 1 (step S37). More specifically, the abort function 44 of the processing circuit 4 substitutes k+1 for k and stores it in the memory circuit.

[0154] Next, it is determined whether k is less than or equal to N (step S39). More specifically, the termination function 44 of the processing circuit 4 determines whether k, which is the number of trials in which the sample droplet SDP was generated, is less than or equal to a specified number, N.

[0155] If it is determined that k is less than or equal to N (step S39: YES), the process returns to step S11 and droplets are generated again. In this embodiment, sample droplets SDP are generated again.

[0156] On the other hand, if it is not determined that k is less than or equal to N (step S39: NO), the process proceeds to step S35. That is, if k, which is the number of trials in which the sample droplet SDP was generated, exceeds the specified number N, the termination function 44 of the processing circuit 4 causes an error message to be output to the output interface 5. After that, step S25 described above is performed.

[0157] The operation of the analytical apparatus 1 according to this embodiment is completed by the above steps.

[0158] Furthermore, the error display in step S35 may include whether the reason for the error is due to the properties of the sample S, contamination of the analyzer 1, a malfunction of the first measuring unit 22, or a malfunction of the second measuring unit 23.

[0159] As explained above, according to this embodiment, by stopping the test when a problem occurs, it is possible to avoid wasting samples and reagents.

[0160] In the above explanation, the term "processor" refers to circuits such as a CPU (Central Processing Unit), a GPU (Graphics Processing Unit), an Application Specific Integrated Circuit (ASIC), or a programmable logic device (e.g., a Simple Programmable Logic Device (SPLD), a Complex Programmable Logic Device (CPLD), and a Field Programmable Gate Array (FPGA)). A processor functions by reading and executing a program stored in a memory circuit. Alternatively, instead of storing the program in a memory circuit, the processor may be configured to directly incorporate the program into its circuitry. In this case, the processor functions by reading and executing the program incorporated into the circuitry. Furthermore, a processor is not limited to being a single circuit; it may also be composed of multiple independent circuits combined to form a single processor and achieve its functions. Additionally, the multiple components shown in Figure 1 may be integrated into a single processor to achieve its functions.

[0161] According to at least one embodiment described above, the influence of the size of the generated droplets on the measurement results regarding the target substance can be reduced.

[0162] Although several embodiments have been described above, these embodiments are presented only as examples and are not intended to limit the scope of the invention. The novel apparatus and methods described herein can be implemented in a variety of other forms. Furthermore, various omissions, substitutions, and modifications can be made to the embodiments of the apparatus and methods described herein, without departing from the spirit of the invention. The appended claims and equivalents are intended to include such embodiments and modifications that are included in the scope and spirit of the invention. [Explanation of Symbols]

[0163] 1 Analyzer 2 Fluid devices 21 Droplet generation section 211 Sample droplet generation unit 212 First reagent droplet generation unit 213 Second reagent droplet generation unit 22 1st measurement section 23 Second measuring section 24 Wastewater section 25 Cleaning solution introduction section 26 Mixing and stirring section 27 Reaction section 28 Heating section 3. Fluid Input / Output Section 4 Processing Circuit 42 Judgment function 43 Analysis Function 44 Cancel function 5 Output Interfaces 62 electrodes DP droplet LQ liquid RDP1 First Reagent Droplet RDP2 Second Reagent Droplet SDP sample droplets

Claims

1. An analytical device that moves a droplet by applying an electric field to perform an analysis of a target substance contained in a sample, A droplet generation means for generating droplets used in the aforementioned analysis, A first measuring means for measuring the size of the aforementioned droplet, A second measuring means for performing measurements related to the target substance using the aforementioned droplet, An analytical means for analyzing the amount of the target substance in the sample based on the measured droplet size and the measurement results regarding the target substance, An analytical device equipped with the following features.

2. The analytical apparatus according to claim 1, wherein the analytical means corrects the measurement results regarding the target substance based on the measured droplet size.

3. The analytical apparatus according to claim 1, wherein the first measuring means comprises an image acquisition unit for acquiring an image of the droplet.

4. The analytical apparatus according to claim 1, wherein the first measuring means comprises an impedance acquisition unit for acquiring the impedance of the droplet.

5. The analytical apparatus according to claim 1, wherein the second measuring means performs at least one of optical measurement, electrochemical measurement, and hue measurement on the droplet.

6. A determination means for determining whether the measured droplet size is within a specified range, If it is determined that the size is not within the specified range, a waste liquid section for discarding the droplet is provided. The analytical apparatus according to claim 1, further comprising:

7. The analytical apparatus according to claim 6, further comprising a channel for sending the droplet to the waste liquid section without passing through the channel to the second measuring means when it is determined that the size is outside the specified range.

8. It is equipped with a plurality of electrodes for applying the aforementioned electric field, The aforementioned plurality of electrodes are A first channel through which a droplet measured by the first measuring means is moved to be measured by the second measuring means, A second channel, different from the first channel, which moves the droplet measured by the first measuring means to the waste liquid section, The analytical apparatus according to claim 7, comprising:

9. If the size is determined to be smaller than the specified range, the droplet generating means further generates a supplement droplet to replenish the droplet, as described in claim 6.

10. The analytical apparatus according to claim 6, further comprising a dividing unit that, when it is determined that the size is larger than the specified range, divides the droplet into a plurality of droplets smaller in size by applying an electric field.

11. The droplet generation means comprises a sample droplet generation means for generating sample droplets containing the sample as droplets, and a reagent droplet generation means for generating reagent droplets containing reagents used for the analysis as droplets. The analytical apparatus according to any one of claims 1 to 10, further comprising a mixing and stirring unit for mixing and stirring the sample droplets and the reagent droplets.

12. The analytical apparatus according to claim 11, further comprising a reaction unit for reacting a mixed droplet of the sample droplet and the reagent droplet.

13. The analytical apparatus according to any one of claims 1 to 10, further comprising a heating unit for heating the aforementioned droplets.

14. The analytical apparatus according to any one of claims 1 to 10, wherein the first measuring means further measures at least one of the movement, mixing, stirring and reaction of the droplet.

15. The analytical apparatus according to any one of claims 1 to 10, further comprising a termination means for suspending the inspection by the analytical apparatus based on at least one of the properties of the sample, contamination of the analytical apparatus, malfunction of the first measuring means, and malfunction of the second measuring means.

16. An analytical method for performing analysis on a target substance contained in a sample by moving a droplet by applying an electric field, A step of generating droplets to be used in the aforementioned analysis, The steps include measuring the size of the aforementioned droplet, A step of performing measurements related to the target substance using the aforementioned droplets, The steps include analyzing the amount of the target substance in the sample based on the measured droplet size and the measurement results regarding the target substance, An analytical method that includes the following features.

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