Electrophoresis Systems
The electrophoresis system addresses the issue of re-carryover by using a sample stage operation that immerses and lifts the capillary end in a cleaning liquid, effectively suppressing carryover and ensuring accurate signal measurement.
Patent Information
- Application Number
- JP2023574964
- Authority / Receiving Office
- JP · JP
- Patent Type
- Patents
- Current Assignee / Owner
- Filing Date
- 2022-01-20
- Publication Date
- 2025-04-21
- Estimated Expiration
- 2042-01-20
AI Technical Summary
Existing electrophoresis systems face challenges in suppressing re-carryover during capillary washing, which can lead to contamination of the cleaning tank and subsequent carryover effects, affecting the accuracy of luminescence signals.
The electrophoresis system incorporates a sample stage operation that reduces carryover by immersing the capillary end in a cleaning liquid and then lifting it up and down, effectively removing residual samples and preventing re-contamination.
This approach significantly suppresses re-carryover, ensuring accurate measurement of fluorescent signals and maintaining the cleanliness of the cleaning container, thereby enhancing the reliability of electrophoresis analysis.
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Abstract
Description
[Technical field]
[0001] The present disclosure relates to electrophoresis systems for analyzing samples using electrophoresis. [Background technology]
[0002] A multi-capillary electrophoresis device is widely used in which multiple capillaries are filled with an electrophoretic separation medium such as an electrolyte solution or an electrolyte solution containing a polymer gel or polymer, and electrophoretic analysis is performed in parallel. The analysis targets in electrophoresis are wide-ranging, from low molecular weight molecules to high molecular weight molecules such as proteins and nucleic acids. There are many measurement modes, such as a mode in which a lamp light is irradiated onto the absorption point of each capillary, and the absorption of the lamp light generated when the analysis target passes through the absorption point is detected, or a mode in which a laser light is irradiated onto the emission point of each capillary, and the fluorescence or scattered light generated when the analysis target passes through the emission point is detected. Therefore, in recent years, there is a demand for an electrophoretic method that can achieve a high dynamic range and high density.
[0003] In electrophoresis systems using capillaries, emission signals may be mixed between multiple capillaries. This is called spatial crosstalk. In addition, when electrophoresis is performed again in a capillary after a sample has been electrophoresed in the capillary, the sample from the previous electrophoresis may remain, making it impossible to obtain an accurate emission signal in the next electrophoresis. This is called carryover.
[0004] The following Patent Document 1 describes a technique for suppressing spatial crosstalk. The document describes the following technique (see abstract): "The present disclosure proposes an electrophoresis system that includes an electrophoresis device having a plurality of capillaries that perform electrophoresis of a sample inside, a light source that irradiates light onto a detection position of the capillaries, a detector that detects light generated by the light source being irradiated and dependent on the components contained in the sample, a buffer storage section into which one end of the plurality of capillaries is inserted during electrophoresis of the sample and in which a buffer is stored, and a computer that controls the electrophoresis device, and the computer controls the electrophoresis conditions of each of the plurality of capillaries in the electrophoresis device so that the arrival times of the components moving in the plurality of capillaries to the detection position are shifted. This makes it possible to detect fluorescent signals at different times in each of the plurality of capillaries in the electrophoresis device (FIG. 4)." (see abstract).
[0005] In order to suppress carryover, it is useful to carry out a step of washing the capillaries. The following Patent Document 2 describes, as an example of a washing step, a technique in which "when the capillary electrophoresis apparatus 1 stops applying high voltage and completes the introduction of the sample into the separation medium in the capillary 31, the autosampler unit 60 moves the table 61 to move the well 71 of the sample plate 73 from the sample introduction end 31a of the capillary 31, and then moves the washing water container 92 to the array position, and immerses the sample introduction end side of the capillary 31 in washing water to remove the sample liquid adhering to the sample introduction end 31a and the outer surface of the conductive member tube 32 (S130)" (see paragraph 0070). [Prior art documents] [Patent documents]
[0006] [Patent Document 1] WO2021 / 210144 A1 [Patent Document 2] JP 2009-042226 A Summary of the Invention [Problem to be solved by the invention]
[0007] It is believed that carry-over can be suppressed to some extent by washing the end of the capillary on the sample introduction side, as in Patent Document 2. On the other hand, the washing tank may be contaminated in the washing process. As a result, even if the washing process is performed in a subsequent measurement, carry-over may occur again due to contamination of the washing tank. Such re-carry-over due to contamination of the washing tank may occur during the course of performing a measurement, and is not adequately addressed in Patent Document 2.
[0008] Carryover may also have an effect on the process of suppressing spatial crosstalk described in Patent Document 1. In Patent Document 1, electrophoresis is controlled so that the time it takes for a component in a first capillary to reach a detection position differs from the time it takes for a component in a second capillary to reach a detection position (see claim 1 in the same document). This is because when a measurement signal from the second capillary is acquired, the signal peak of carryover when the first capillary is used and the signal peak of spatial crosstalk from the second capillary may overlap each other on the time axis.
[0009] The present disclosure has been made in consideration of the above-mentioned problems, and has an object to provide an electrophoresis system capable of suppressing re-carryover that occurs when cleaning a capillary. [Means for solving the problem]
[0010] The electrophoresis system according to the present disclosure causes the sample stage to perform an operation to reduce carryover that affects analysis of a sample using a second capillary of the plurality of capillaries due to the sample remaining in a washing container after the sample is introduced into a first capillary of the plurality of capillaries. Effect of the Invention
[0011] According to the electrophoresis system of the present disclosure, it is possible to suppress re-carryover that occurs when cleaning the capillaries. Other configurations, problems, advantages, and the like of the present disclosure will become apparent from the description of the following embodiments. [Brief description of the drawings]
[0012] [Figure 1] FIG. 1 is a configuration diagram of an electrophoresis system 1 according to a first embodiment. [Diagram 2] 1 is a graph showing an example of carryover. [Diagram 3] FIG. 1 is a plan view illustrating a method for suppressing spatial crosstalk in Patent Document 1. [Figure 4] 1 shows an example in which carryover signal peaks and spatial crosstalk signal peaks overlap on the time axis. [Diagram 5] FIG. 1 is a schematic diagram showing a method for suppressing carryover in embodiment 1. [Figure 6] FIG. 2 is a schematic diagram showing another method for suppressing carryover in embodiment 1. [Figure 7] FIG. 2 is a schematic diagram showing another method for suppressing carryover in embodiment 1. [Figure 8] FIG. 2 is a schematic diagram showing another method for suppressing carryover in embodiment 1. [Figure 9] FIG. 2 is a schematic diagram showing another method for suppressing carryover in embodiment 1. [Figure 10] 1 is a graph showing the results of verifying the effect of suppressing carryover in embodiment 1. [Figure 11] 1 is a graph showing the results of verifying the effect of suppressing carryover in embodiment 1. [Figure 12] 1 is a time chart of each process when a procedure for suppressing carryover is incorporated into a normal measurement process. [Figure 13]11 is a time chart of each step when a procedure for suppressing carryover is incorporated into a calibration step for suppressing spatial crosstalk. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS
[0013] <First embodiment: System configuration> 1 is a configuration diagram of an electrophoresis system 1 according to a first embodiment of the present disclosure. The electrophoresis system 1 is composed of an electrophoresis device 100 and an arithmetic device 200 (computer). The electrophoresis device 100 is a device that analyzes components contained in a sample by electrophoresing the sample using capillaries.
[0014] The electrophoresis apparatus 100 includes a detection unit 116, a thermostatic bath 118, a transport machine 125, a high-voltage power supply 104, a first ammeter 105, a second ammeter 112, a capillary 102, and a pump mechanism 103. The detection unit 116 optically detects a sample. The thermostatic bath 118 keeps the capillary 102 at a constant temperature. The transport machine 125 transports various containers to the cathode end of the capillary. The high-voltage power supply 104 applies a high voltage to the capillary 102. The first ammeter 105 measures the current output by the high-voltage power supply 104. The second ammeter 112 measures the current flowing through the anode electrode 111. The pump mechanism 103 injects a polymer into the capillary 102.
[0015] The capillary 102 is made of a glass tube with an inner diameter of several tens to several hundreds of microns and an outer diameter of several hundreds of microns, and its surface is coated with polyimide to improve its strength. However, the polyimide coating is removed from the light irradiated portion where the laser light is irradiated so that the light emitted from inside can easily leak to the outside. The inside of the capillary 102 is filled with a separation medium for imparting a difference in migration speed during electrophoresis. There are two types of separation medium: fluid and non-fluid, but in this embodiment 1, a fluid polymer is used.
[0016] The detection unit 116 is a partial region of the capillary 102. When the detection unit 116 is irradiated with excitation light from the light source 114, fluorescence having a wavelength dependent on the sample (hereinafter referred to as information light) is generated from the sample and emitted outside the capillary 102. The information light is split into wavelength directions by the diffraction grating 132. The optical detector 115 analyzes the sample by detecting the split information light.
[0017] The capillary cathode ends 127 are fixed through respective metallic hollow electrodes 126, and the capillary tips protrude about 0.5 mm from the hollow electrodes 126. All of the hollow electrodes 126 provided for each capillary are mounted integrally on a load header 129. All of the hollow electrodes 126 are electrically connected to the high-voltage power supply 104 mounted on the main body of the apparatus, and when it is necessary to apply voltage for electrophoresis, sample introduction, etc., the hollow electrodes 126 operate as cathode electrodes.
[0018] The capillary cathode end 127 and the opposite capillary end (the other end) are bound together by a capillary head 133. The capillary head 133 can be connected to the block 107 in a pressure-tight manner. A high voltage output from a high-voltage power supply 104 is applied between the load header 129 and the capillary head 133. A syringe 106 fills new polymer into the capillary from the other end. The polymer in the capillary is refilled for each measurement to improve the measurement performance.
[0019] The pump mechanism 103 is composed of a syringe 106 and a mechanism for pressurizing the syringe 106. The block 107 is a connection member for communicating the syringe 106, the capillary 102, the anode buffer container 110, and the polymer container 109 with each other.
[0020] The optical detection section that detects information light from the sample is composed of a light source 114, an optical detector 115 for detecting luminescence in the detection section 116, and a diffraction grating 132. When detecting a sample in a capillary separated by electrophoresis, the light source 114 irradiates the detection section 116 of the capillary, the luminescence from the detection section 116 is dispersed by the diffraction grating 132, and the optical detector 115 detects the dispersed information light.
[0021] The thermostatic chamber 118 is covered with a heat insulating material to keep the inside at a constant temperature, and the temperature is controlled by a heating and cooling mechanism 120. A fan 119 circulates and stirs the air in the thermostatic chamber 118, and keeps the temperature of the capillary 102 uniform and constant at various positions.
[0022] The transporter 125 is equipped with up to three electric motors and linear actuators, and can move in up to three axes, up and down, left and right, and in the depth direction. At least one or more containers can be placed on a stage 130 of the transporter 125. The stage 130 is equipped with an electric grip 131, and a user can grasp and release each container through the grip 131. This allows the buffer container 121, the washing container 122, the waste liquid container 123, and the sample container 124 to be transported to the capillary cathode end 127 as needed. Unnecessary containers are stored in a designated storage location within the device. The buffer container 121 and the washing container 122 are sometimes collectively referred to as a "buffer storage section."
[0023] The arithmetic device 200 obtains the detection result of the information light from the optical detector 115, and performs processing such as creating a fluorescence intensity waveform (described later) by analyzing the result, and calculating the base length of the substance to be measured. Details of the processing performed by the arithmetic device 200 and other components shown in Fig. 1 will be described later. The arithmetic device 200 can be configured, for example, by a Central Processing Unit (CPU) and software executed by the CPU, or can be configured by hardware such as a circuit device implementing similar functions.
[0024] <First embodiment: Problems with the prior art> FIG. 2 is a graph showing an example of carryover. As described in 0070 of Patent Document 2, carryover can be suppressed to some extent by immersing the tip of the capillary in the washing container 122. However, this washing operation may also contaminate the inside of the washing container 122. If this happens, the next time the tip of the capillary is immersed in the washing container 122, carryover will occur again due to contamination of the washing container 122. This re-carryover may reach, for example, about 0.3% of the fluorescent signal peak in the previous measurement, and may become an obstacle to accurate measurement of the fluorescent signal peak. Therefore, it is necessary to suppress contamination of the washing container 122.
[0025] Fig. 3 is a plan view illustrating a method for suppressing spatial crosstalk in Patent Document 1. Here, the sample container 124 has 8 x 8 = 64 wells, and a case is illustrated in which a sample and a buffer (or a hollow) are contained as shown in Fig. 3. Eight capillaries are lined up in the Y direction, and the eight capillaries are simultaneously inserted into the sample container 124 to inject a sample or a buffer into each capillary (nothing is injected in the case of a hollow capillary).
[0026] When a sample is injected into the first capillary (the sample in the upper left of FIG. 3), the sample is not injected into the second to eighth capillaries. Similarly, when a sample is injected into the second capillary, the sample is not injected into the first and third to eighth capillaries. This causes a difference between the timing at which the sample components in the first capillary reach the detection unit 116 and the timing at which the sample components in the second capillary reach the detection unit 116. Therefore, spatial crosstalk between the capillaries can be suppressed. However, when this method is used, if carryover occurs, the following inconveniences occur.
[0027] Figure 4 shows an example where carryover signal peaks and spatial crosstalk signal peaks overlap on the time axis. In the method shown in Figure 3, assume that a first sample (the sample at the top left in Figure 3) is introduced into the first capillary and electrophoresis is performed to analyze the sample components, resulting in the identification of four signal peaks shown at the left end of the first sample. The timing of introducing the next second sample into the second capillary is shifted from the timing of introducing the sample into the first capillary, as shown in the lower part of Figure 4, so that the signal peaks in each capillary do not overlap on the time axis.
[0028] However, due to the influence of carryover (including carryover in the first capillary, carryover in the washing container 122, etc.) when the first sample is introduced into the first capillary, the carryover signal peak may overlap on the time axis with the fluorescence signal peak when the sample components are analyzed using the second capillary. If these overlap, the signal peaks will be read erroneously, hindering accurate component analysis.
[0029] In Fig. 3, an example is described in which the timing of introducing the sample into each capillary is made different between the capillaries, but the method of suppressing spatial crosstalk is not limited to this. Other methods may be used as long as the timing at which the sample components reach the detection unit 116 can be made different between the capillaries. Patent Document 1 describes an example in which the temperature and concentration of the buffer solution are changed for each well. It should be noted that even in this case, the same problem as in Fig. 4 occurs.
[0030] <Embodiment 1: Method for suppressing carryover> Fig. 5 is a schematic diagram showing a method for suppressing carryover in the present embodiment 1. Here, an example of performing a step of suppressing carryover when performing a procedure for suppressing spatial crosstalk as described in Fig. 3 will be described, but the procedure for suppressing carryover is not limited to this and can also be performed in a general measurement procedure. A specific example will be described later.
[0031] 5, the computing device 200 controls the stage 130 so that, after the sample is introduced into the first capillary ((1)) and before electrophoresis is performed in the first capillary ((3)), the end of the first capillary on the sample introduction side is immersed in the cleaning liquid in the cleaning container 122 and then pulled up from the cleaning container 122 at least once ((2)). By moving the capillary end in and out of the cleaning liquid, it is believed that the cleaning effect is improved compared to when the capillary end is simply immersed in the cleaning liquid. This is believed to be because the residual sample attached to the lid that seals the top of the cleaning container 122 is removed when the capillary end is pulled up from the cleaning container 122.
[0032] FIG. 6 is a schematic diagram showing another method of suppressing carryover in the first embodiment. In this example, unlike FIG. 5, the capillary is inserted into and removed from the cleaning solution immediately after performing electrophoresis. Specifically, the procedure is as follows. After the arithmetic device 200 introduces a sample into the first capillary ((1)), the arithmetic device 200 cleans the end of the first capillary on the sample introduction side by immersing it in the cleaning solution in the cleaning container 122 ((2)), and then performs electrophoresis in the first capillary ((3)). After performing electrophoresis in the first capillary, the arithmetic device 200 controls the stage 130 so that the end of the first capillary on the sample introduction side is inserted into and removed from the cleaning solution ((4)) until the sample is introduced into the second capillary ((5)). This allows the capillary to be effectively cleaned, similar to FIG. 5.
[0033] FIG. 7 is a schematic diagram showing another method of suppressing carryover in the first embodiment. In FIG. 7, the sample container 124 has alternating rows in which only one well containing a sample is arranged and the rest are not sample wells, and rows in which only wells containing blank samples are arranged. A blank sample is a liquid that is contained in the sample container 124 but is not a sample. The position of the well containing the sample moves one to the left every two rows. In this example, the cleaning effect is enhanced by immersing the capillary in a blank sample in addition to immersing it in a cleaning liquid.
[0034] 7, the arithmetic device 200 controls the stage 130 so that the end of the first capillary on the sample introduction side is immersed in a blank sample ((2)) after the sample is introduced into the first capillary ((1)) and before electrophoresis is performed in the first capillary ((4)). In this example, the arithmetic device 200 further controls the stage 130 so that the end of the first capillary on the sample introduction side is immersed in a cleaning solution in the cleaning container 122 during the period from when the first capillary is immersed in the blank sample to when electrophoresis is performed in the first capillary ((4)). By using both the cleaning solution and the blank sample, the cleaning effect can be improved.
[0035] In the example shown in FIG. 7, the sample container 124 containing the blank sample is not reused, and when electrophoresis is completed for all samples in the sample container 124, the blank sample is discarded together with the sample container 124. Therefore, unlike the washing container 122, contamination does not accumulate in the blank well. Therefore, the up and down movement of the washing container 122 described in FIG. 5 to FIG. 6 is not essential. However, since it is necessary to place a blank well in the sample container 124, the number of sample wells that can be placed is reduced accordingly. On the other hand, in a use case in which not all of the wells in the sample container 124 are used, there is no particular disadvantage in using the example shown in FIG. 7, and the washing effect can be effectively exerted.
[0036] Fig. 8 is a schematic diagram showing another method for suppressing carryover in the first embodiment. The procedure in Fig. 8 is obtained by interchanging steps (2) and (3) in Fig. 7. That is, after a sample is introduced into the first capillary ((1)), the first capillary is immersed in a cleaning solution ((2)), and then the first capillary is immersed in a blank sample ((3)). The other steps are the same as those in Fig. 7. This procedure can also achieve the same cleaning effect as in Fig. 7.
[0037] FIG. 9 is a schematic diagram showing another method of suppressing carryover in the first embodiment. The arrangement of the samples and blank samples is the same as in FIG. 7 to FIG. 8. In the example shown in FIG. 9, after performing electrophoresis using the first capillary ((3)), until performing electrophoresis using the second capillary ((7)), the calculation device 200 immerses the first capillary in the blank sample ((4)), and then immerses the first capillary in the cleaning solution ((5)). Furthermore, by performing electrophoresis ((6)), the carryover components remaining in the first capillary are flushed away. It is considered that the carryover can be effectively suppressed before the electrophoresis of the second capillary by washing the first capillary with the blank sample and the cleaning solution immediately after the electrophoresis. Furthermore, by performing electrophoresis to flush away the carryover components before the electrophoresis of the second capillary, the suppression effect can be enhanced.
[0038] Fig. 10 is a graph showing the results of verifying the effect of suppressing carryover in the present embodiment 1. The upper part of Fig. 10 shows the results of re-measuring the fluorescent signal peaks in a capillary that has undergone electrophoresis and been washed by immersing it in a washing solution. The vertical axis shows the ratio of the carryover signal peak to the signal peak during electrophoresis. In the example shown in the upper part of Fig. 10, the CH3 capillary shows a carryover of about 0.2%.
[0039] The bottom part of Figure 10 shows the results of measuring the carryover ratio when the procedure explained in Figure 5 was carried out under the same conditions as the top part of Figure 10. It can be seen that the carryover in CH3 was reduced to below the detection limit. Therefore, it can be said that carryover can be sufficiently suppressed by immersing the tip of the capillary in the cleaning solution and moving it up and down as explained in Figure 5.
[0040] Fig. 11 is a graph showing the results of verifying the effect of suppressing carryover in the present embodiment 1. In this example, carryover could not be sufficiently suppressed when the capillary tip was only immersed in the cleaning solution (without vertical movement) as in the conventional method, and when only the vertical movement shown in Fig. 6 was performed. In contrast, it was confirmed that the cleaning operation described in Fig. 9 and the cleaning operation using Fig. 9 and Fig. 6 in combination could suppress carryover to below the detection limit.
[0041] <First embodiment: Summary> The electrophoresis system 1 according to the first embodiment reduces carryover from the first sample to such an extent that the sample remaining in the washing container 122 after the sample is introduced into the first capillary does not affect the analysis of the sample using the second capillary. Specifically, the stage 130 is controlled to perform the operations described in Figs. 5 to 9. This makes it possible to effectively suppress re-carryover caused by washing the capillary.
[0042] The electrophoresis system 1 according to the first embodiment suppresses spatial crosstalk by making the timing of the sample signal peaks different between the capillaries, and further suppresses carryover between samples by the method described in Fig. 5 to Fig. 9. This makes it possible to suppress the influence of carryover that remains even when spatial crosstalk is avoided, as described in Fig. 4. Therefore, the effect of suppressing spatial crosstalk can be reliably achieved.
[0043] <Embodiment 2> In the first embodiment, several examples of the method for suppressing carryover between samples are described. These procedures can be incorporated into a normal measurement process for measuring sample components using electrophoresis, or can be incorporated into a calibration process for suppressing spatial crosstalk as in Patent Document 2. In the second embodiment of the present disclosure, specific examples of these procedures are described.
[0044] FIG. 12 is a time chart of each step in the case where a procedure for suppressing carryover is incorporated into a normal measurement step. In a measurement step using general electrophoresis, a separation medium such as a polymer is introduced into a capillary, a preliminary run is performed, and then a sample is introduced into the capillary and electrophoresis is performed. These four steps are repeated. Carryover can be suppressed by performing the steps explained in FIG. 5 to FIG. 9 during the period from when the sample is introduced into the first capillary until the measurement step using the second capillary is started (the electrophoresis step of Run 2 in FIG. 12). For example, it may be performed in the electrophoresis step of Run 1. All of the steps explained in FIG. 5 to FIG. 9 are performed following (1) Injection-1, and therefore have in common that they are performed in the electrophoresis step of Run 1.
[0045] The first sample injection step in Fig. 12 corresponds to (1) Injection-1 in Figs. 5 to 9. In the next electrophoresis step, steps (2) and after in Figs. 5 to 9 are carried out. The second polymer injection step to sample injection step correspond to Injection-2 in Figs. 5 to 9, so it is sufficient to complete steps (2) to just before Injection-2 in Figs. 5 to 9 at least before starting these steps.
[0046] FIG. 13 is a time chart of each step in the case where a procedure for suppressing carryover is incorporated into a calibration step for suppressing spatial crosstalk. The calibration step described in Patent Document 2 suppresses spatial crosstalk while repeating electrophoresis while proceeding one by one through the rows of wells in the sample container 124 shown in FIG. 5, for example. Therefore, as shown in FIG. 13, the samples in each row are repeatedly introduced into the capillaries and electrophoresed. In this calibration step, each method described in the first embodiment can be used. That is, carryover can be suppressed by performing the procedures described in FIG. 5 to FIG. 9 during the period from when the sample is introduced into the first capillary until the measurement step using the second capillary is started (the electrophoresis step of Run 2 in FIG. 12). For example, it may be performed in the electrophoresis step using the first capillary.
[0047] The first sample injection step in Fig. 13 corresponds to (1) Injection-1 in Figs. 5 to 9. In the next electrophoresis step, steps (2) and after in Figs. 5 to 9 are carried out. The second sample injection step corresponds to Injection-2 in Figs. 5 to 9, so it is sufficient to complete at least steps (2) to just before Injection-2 in Figs. 5 to 9 before starting these steps.
[0048] <Embodiment 2: Summary> As described in the present embodiment 2, the carryover suppression procedure according to the present disclosure can be performed (a) for each run during the polymer injection to electrophoresis in the normal measurement process, or (b) for each sample injection in the calibration process exemplified in Patent Document 2. Even when performed for each run, the effect of spatial crosstalk may occur, so the carryover suppression procedure according to the present disclosure is useful for suppressing this. Furthermore, even if calibration is performed to suppress spatial crosstalk as described in Patent Document 2, slight crosstalk may remain, so the carryover suppression procedure according to the present disclosure is useful for suppressing this.
[0049] <Modifications of the present disclosure> The present disclosure is not limited to the above-described embodiments, and includes various modified examples. For example, the above-described embodiments have been described in detail to clearly explain the present disclosure, and are not necessarily limited to those having all of the configurations described. In addition, it is possible to replace a part of the configuration of one embodiment with the configuration of another embodiment, and it is also possible to add the configuration of another embodiment to the configuration of one embodiment. In addition, it is possible to add, delete, or replace a part of the configuration of each embodiment with another configuration.
[0050] In the above embodiments, carryover does not necessarily need to be strictly zero, but may be suppressed to a level that does not interfere with the measurement of sample components. For example, with respect to carryover when measuring the second sample described in FIG. 4, it is sufficient to suppress carryover to a level that allows the sample components to be measured after identifying the respective sample signal peaks of the second sample.
[0051] In the above embodiment, an example of a sample measured by the electrophoresis device 100 is a DNA fragment, but is not limited thereto. The present disclosure can also be applied to other samples. That is, the present disclosure can be applied to a sample that is quantified through electrophoresis when carryover between samples is suppressed. [Explanation of symbols]
[0052] 1: Electrophoresis system 100: Electrophoresis device 122: Cleaning container 124: Sample container 130: Stage 200: Arithmetic device
Claims
1. An electrophoresis system comprising an electrophoresis apparatus and a computer that controls the electrophoresis apparatus, The electrophoresis device comprises: a plurality of capillaries within which the sample is electrophoresed; a light source that irradiates light onto a detection position of the capillary; a detector for detecting signal light generated depending on components contained in the sample when the light from the light source is irradiated onto the sample; a cleaning vessel containing a cleaning liquid for cleaning the capillaries; a stage for changing a position of the cleaning container relative to the plurality of capillaries by moving the cleaning container; Equipped with the computer causes the stage to perform an operation to reduce carryover, which is an effect of the sample remaining in the washing container after the sample is introduced into a first capillary among the plurality of capillaries when the sample is analyzed using a second capillary among the plurality of capillaries; The electrophoresis apparatus further includes a washing tank containing a washing solution, The computer controls the stage to move the end of the first capillary in and out of the washing tank during the period from when the sample is injected into the first capillary until electrophoresis is performed in the first capillary, thereby reducing the carryover. Electrophoresis system comprising:
2. An electrophoresis system comprising an electrophoresis apparatus and a computer that controls the electrophoresis apparatus, The electrophoresis device comprises: a plurality of capillaries within which the sample is electrophoresed; a light source that irradiates light onto a detection position of the capillary; a detector for detecting signal light generated depending on components contained in the sample when the light from the light source is irradiated onto the sample; a cleaning vessel containing a cleaning liquid for cleaning the capillaries; a stage for changing a position of the cleaning container relative to the plurality of capillaries by moving the cleaning container; Equipped with the computer causes the stage to perform an operation to reduce carryover, which is an effect of the sample remaining in the washing container after the sample is introduced into a first capillary among the plurality of capillaries when the sample is analyzed using a second capillary among the plurality of capillaries; The electrophoresis apparatus further includes a washing tank containing a washing solution, The computer controls the stage to move the end of the first capillary in and out of the washing tank during the period from when electrophoresis is performed in the first capillary to when the sample is injected into the second capillary, thereby reducing the carryover. Electrophoresis system comprising:
3. An electrophoresis system comprising an electrophoresis apparatus and a computer that controls the electrophoresis apparatus, The electrophoresis device comprises: a plurality of capillaries within which the sample is electrophoresed; a light source that irradiates light onto a detection position of the capillary; a detector for detecting signal light generated depending on components contained in the sample when the light from the light source is irradiated onto the sample; a cleaning vessel containing a cleaning liquid for cleaning the capillaries; a stage for changing a position of the cleaning container relative to the plurality of capillaries by moving the cleaning container; Equipped with the computer causes the stage to perform an operation to reduce carryover, which is an effect of the sample remaining in the washing container after the sample is introduced into a first capillary among the plurality of capillaries when the sample is analyzed using a second capillary among the plurality of capillaries; The electrophoresis apparatus further includes a blank container containing a blank sample, The computer controls the stage to immerse the end of the first capillary in the blank sample during the period from when the sample is injected into the first capillary until when electrophoresis is performed in the first capillary, thereby reducing the carryover. Electrophoresis system comprising:
4. An electrophoresis system comprising an electrophoresis apparatus and a computer that controls the electrophoresis apparatus, The electrophoresis device comprises: a plurality of capillaries within which the sample is electrophoresed; a light source that irradiates light onto a detection position of the capillary; a detector for detecting signal light generated depending on components contained in the sample when the light from the light source is irradiated onto the sample; a cleaning vessel containing a cleaning liquid for cleaning the capillaries; a stage for changing a position of the cleaning container relative to the plurality of capillaries by moving the cleaning container; Equipped with the computer causes the stage to perform an operation to reduce carryover, which is an effect of the sample remaining in the washing container after the sample is introduced into a first capillary among the plurality of capillaries when the sample is analyzed using a second capillary among the plurality of capillaries; The electrophoresis apparatus further includes a blank container containing a blank sample and a washing tank containing a washing solution, The computer performs the following during the period from when electrophoresis is performed in the first capillary to when the next electrophoresis is performed in the second capillary: Immersing an end of the first capillary into the blank sample; Immersing an end of the first capillary in the cleaning solution; Electrophoresis is performed in the first capillary to flush away the sample remaining in the first capillary. The stage is controlled so that Electrophoresis system comprising:
5. The computer controls the stage to suppress spatial crosstalk between the first capillary and the second capillary.
5. The electrophoresis system according to claim 1, wherein the electrophoresis system comprises:
6. The computer controls the stage so that the timings of injecting the sample into the capillaries differ between the first capillary and the second capillary, thereby suppressing the spatial crosstalk.
6. The electrophoresis system according to claim 5.
7. The computer controls the electrophoresis device so that the timings at which the components moving inside the capillaries reach the detection position differ between the first capillary and the second capillary, thereby suppressing the spatial crosstalk.
6. The electrophoresis system according to claim 5.
8. the computer controls the stage such that a signal peak of a component measured by the first capillary avoids a signal peak of the spatial crosstalk from the second capillary; The computer controls the stage to reduce the carryover from the first capillary to an extent that a signal peak of the spatial crosstalk from the second capillary can be identified.
6. The electrophoresis system according to claim 5.
9. The electrophoresis apparatus further includes a washing tank containing a washing solution, The computer controls the stage so that the end of the first capillary is immersed in the cleaning solution during the period from when the first capillary is immersed in the blank sample to when electrophoresis is performed in the first capillary.
4. The electrophoresis system according to claim 3.
10. The electrophoresis apparatus further includes a washing tank containing a washing solution, The computer controls the stage so that the end of the first capillary is immersed in the cleaning liquid during the period from when the sample is injected into the first capillary until when the end of the first capillary is immersed in the blank sample.
4. The electrophoresis system according to claim 3.
11. The computer causes the stage to perform an operation for reducing the carryover during the process of measuring the sample using the capillary.
5. The electrophoresis system according to claim 1, wherein the electrophoresis system comprises:
12. The computer causes the stage to perform an operation for reducing the carryover in a calibration step before measuring the sample using the capillary.
5. The electrophoresis system according to claim 1, wherein the electrophoresis system comprises:
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