JP2009174995A - Channel structure, channel substrate and fluid control method - Google Patents

Abstract

Provided is a flow channel structure that can process a sample with high accuracy and efficiency when a sample is processed using a plurality of flow channels.
A flow path structure including a plurality of flow paths each including at least a sample introduction section for introducing a sample, a processing section for processing the sample, and a discharge section for discharging the sample. The path includes a sheath liquid introduction part that introduces a sheath liquid into the sample introduced from the sample introduction part, and the distance from the joining part of the flow path and the sheath liquid introduction part to the processing part is substantially equal in each flow path. Use a channel structure that is distance.
[Selection] Figure 2

Description

  The present invention relates to a channel structure, a channel substrate, and a fluid control method.

  A technique for flowing a small amount of sample through a microchannel and analyzing the sample in the channel has been applied to a wide range of fields including bio-related analysis and chemical analysis. For example, it is used for trace chemical analysis of biological substances and substances in the natural environment.

  An example of such a technique is flow cytometry. In flow cytometry, cells, proteins, beads, etc. are targeted as samples, and these analyzes are performed in the flow path. Based on the results of this analysis, the sample is subsequently collected. In order to accurately sort the sample, it is important to continue conveying the sample in the channel quantitatively and precisely.

  As other fields, for example, a measurement technique in such a flow channel is applied as a microsystem technique in chemical analysis or the like. For example, an application to a microchemical analysis system or the like in which a similar microchannel is provided as a fluid element on a substrate and various detectors are integrated is considered.

  However, a particular problem with such a flow channel structure is the occurrence of turbulence due to changes in velocity distribution due to flow rate, etc., and it is known that transition from laminar flow to turbulent flow has a significant effect. It has been. Furthermore, it is necessary to prevent samples in the flow channel, particularly biomaterials, from coming into contact with the flow channel wall surface. In order to solve such a problem, for example, in flow cytometry or the like, a predetermined flow path structure is formed on a substrate, and a sample is sandwiched between so-called sheath liquids and sent.

  An example of the prior art relating to such a flow channel structure will be described with reference to FIG. Reference numeral 9 in FIG. 9 shows an example of a conventional flow path substrate. The flow path substrate 9 includes nine sample introduction portions 91a, 91b, 91c, 91d, 91e, 91f, 91g, 91h, and 91i (hereinafter sometimes collectively referred to as sample introduction portions 91). The sample introduced from each sample introduction part 91 is sandwiched by the sheath liquid from the sheath liquid introduction part 92 via the introduction flow path 921 and the flow paths 93, 93 and conveyed through the flow path 94. Through the introduction channel 921 having a large channel width and depth, the sheath liquid is sent from one sheath liquid introduction unit 92 to each channel. In the processing unit 95, each sample is subjected to measurement such as fluorescence analysis and scattered light analysis. Thereafter, the fluid is discharged and collected from the corresponding discharge portions 97a to 97i through the flow path 96. As described above, by arranging a plurality of flow paths in parallel, there are advantages that a plurality of samples can be performed at a time.

  Patent Document 1 discloses an analyzer that can easily and efficiently measure a plurality of samples. A structure in which a plurality of flow paths provided with a reaction chamber for storing solid particles and a detection unit for optically analyzing a solution flowing out of the reaction chamber are arranged in parallel is disclosed. And the idea etc. which make the space | interval of a some sample solution introducing | transducing part wider than the width | variety of the flow path currently arranged in parallel by the detection part are indicated.

Japanese Patent Application Laid-Open No. 2004-301733.

  However, when measurement is performed by arranging such channels in parallel, the accuracy is affected unless the channel length from the introduction of the sample into the channel to the measurement is uniform. When the channel length is different, the pressure in the channel, the flow rate of the sample, and the like are different, resulting in variations in sample processing conditions. The above problem is particularly noticeable when a plurality of samples are processed in a minute flow path.

  Therefore, a main object of the present invention is to provide a flow channel structure that can be processed with high accuracy and efficiency when a sample is processed using a plurality of flow channels.

First, the present invention is a flow channel structure including a plurality of flow channels each including at least a sample introduction unit for introducing a sample, a processing unit for processing the sample, and a discharge unit for discharging the sample. The channel includes a sheath liquid introduction part that introduces a sheath liquid into the sample introduced from the sample introduction part, and the distance from the joining part of the flow path and the sheath liquid introduction part to the processing part is substantially equal in each flow path. A flow path structure is provided. By making the distance from the joining part with the sheath liquid introduction part in each channel to the processing unit substantially equal, it is possible to prevent variations in processing conditions in the processing unit of each channel. In the present invention, the distance refers to the length of the flow path (flow path length) unless otherwise specified.
Next, the present invention provides a flow channel structure in which at least two or more flow channels introduce a sample into each flow channel from the same sample introduction unit. In a flow channel structure having a plurality of flow channels, the structural restriction can be relaxed by sharing the sample introduction part.
And this invention provides the flow-path structure which introduce | transduces a sheath liquid into each flow path from the same sheath liquid introduction part at least 2 or more flow paths. In the flow channel structure including a plurality of flow channels, the structural restriction can be relaxed by sharing the sheath liquid introduction part.
Further, according to the present invention, the sheath liquid introduction part of the flow path is provided with a first sheath liquid introduction part for introducing the first sheath liquid into the sample introduced from the sample introduction part and the first sheath liquid. At least a second sheath liquid introduction part for introducing the second sheath liquid from a direction different from the introduction direction of the first sheath liquid with respect to the sample, the flow path and the second sheath liquid introduction part Provided is a channel structure in which the distance from the merging unit to the processing unit is substantially equal in each channel. Since it is possible to introduce not only the first sheath liquid but also the second sheath liquid, a laminar flow of the sample can be created with high accuracy at an arbitrary position in the flow path.
Further, the present invention is a flow channel structure including a plurality of flow channels each including at least a sample introduction unit that introduces a sample, a processing unit that processes the sample, and a discharge unit that discharges the sample. Provided is a channel structure in which the distance from the introduction unit to the processing unit is substantially equal in each channel. By setting the distance from the confluence portion with the sample introduction portion in each channel to the processing portion at least approximately equal, it is possible to prevent variations in processing conditions in the processing portion of each channel.
The present invention is a flow path substrate including a plurality of flow paths each including at least a sample introduction section for introducing a sample, a processing section for processing the sample, and a discharge section for discharging the sample. The channel includes a sheath liquid introduction part that introduces a sheath liquid into the sample introduced from the sample introduction part, and the distance from the joining part of the flow path and the sheath liquid introduction part to the processing part is substantially equal in each flow path. A flow path substrate is provided.
Furthermore, in the above-described flow channel structure, the present invention adjusts at least one of the width and / or depth of the flow channel, the width and / or depth of the sheath liquid introduction part, the flow rate of the sample, and the flow rate of the sheath liquid. Thus, a control method for controlling the position of the sample in the flow path is provided. Since the flow path structure in which the distance from the confluence part with the sheath liquid introduction part in each flow path to the processing part is substantially equidistant, the width and depth of the flow path and the sheath liquid introduction part, the flow rate of the sample and the sheath liquid By adjusting, the position of the sample in the flow path can be controlled with high accuracy.

  According to the present invention, a sample can be processed using a plurality of channels with high accuracy and efficiency.

  Hereinafter, preferred embodiments of a flow channel structure according to the present invention will be described with reference to the accompanying drawings. Each embodiment shown in the accompanying drawings shows an example of a typical embodiment according to the present invention, and the scope of the present invention is not interpreted narrowly. In the drawings used below, for the convenience of explanation, the configuration of the apparatus is shown in a simplified manner.

  FIG. 1 is a conceptual diagram of a first embodiment of a flow channel structure according to the present invention. Reference numeral 1 in FIG. 1 indicates the flow channel structure according to the present invention. The size, shape, and the like of the flow channel structure 1 can be appropriately designed according to the purpose.

  The flow channel structure 1 includes nine sample introduction portions 11a, 11b, 11c, 11d, 11e, 11f, 11g, 11h, and 11i (hereinafter, sometimes collectively referred to as the sample introduction portion 11) and one sheath. The liquid introduction part 12, the process part 13, and the discharge part 14 are provided. The sample introduction unit 11 and the processing unit 13 communicate with each other through the main channel 15, and the processing unit 13 and the discharge unit 14 communicate with each other through the channel 16.

  The sheath liquid introduction part 12 communicates with the main flow path 15 at the merge part 18 via the sheath liquid flow paths 17 and 17. The sheath liquid channels 17 and 17 are arranged so as to face each other with the main channel 15 interposed therebetween. Then, the sheath liquid can be fed into each sheath liquid flow path 17 from one sheath liquid introducing portion 12 through the introduction flow path 121. The introduction channel 121 is a channel having a channel width and a channel depth larger than those of other channels, and can supply sheath liquid from the sheath liquid supply unit 1211 to each channel. Thereby, it is not necessary to provide a sheath liquid introduction port in each of the sheath liquid supply parts 1211, and structural restrictions can be relaxed.

  In the present invention, the type of sample is not particularly limited, and may be, for example, a microparticle such as a cell, protein, or bead, or a fluid such as various antibodies or reagents.

  In the present invention, the type of the sheath liquid is not limited, and any substance can be used as long as the target sample can be sandwiched and conveyed. In other words, the present invention can be used in various fields as a technique related to fluid control, and a sample and a sheath liquid can be selected according to the application. Therefore, a suitable fluid can be selected as appropriate in consideration of the properties of the sample used. Moreover, you may add an additive etc. as needed.

  For example, in the field of flow cytometry, cells, proteins, beads or the like can be used as a sample, and a sheath liquid such as physiological saline can be used as a fluid. In addition, when used as various analyzers and microreactors, various oils, organic solvents, electrolytes, etc. are used as sheath liquids, so that nanoemulsions, nanocapsules, crystallization of various samples, chemical synthesis of hazardous substances, etc. And component analysis are possible.

  The sample introduced from the sample introduction unit 11 is conveyed through the main flow path 15. The sheath liquid introduced from the sheath liquid introduction part 12 is conveyed through the sheath liquid flow paths 17 and 17 and is introduced so as to sandwich the sample in the main flow path 15 from the left and right at the joining part 18.

  Thereby, it can prevent that a sample collides with a flow-path wall surface, or adheres. In general, the velocity distribution in the cross section of the flow path is slow on the wall surface inside the flow path and becomes fast at the center of the flow path according to the Hagen-Poiseuille principle. In this regard, in the flow channel structure according to the present invention, the sample can pass through the central portion in the flow channel.

  Furthermore, it is possible to prevent the sample from adhering to the wall surface of the channel and blocking the channel. Thereby, it is possible to obtain excellent stability with respect to the flow rate of the sample, the position of the sample in the flow path, the order of the samples to be transported, and the like. The sample flow rate can also be kept constant in the flow path.

  The sample into which the sheath liquid has been introduced at the merging portion 18 is transported through the main flow path 15 and is subjected to various processes in the processing portion 13. The content of the “treatment” performed in the present invention is not limited, and includes, for example, various measurement / detection / separation / reaction processes.

  For example, when measurement / detection is performed by the processing unit 13, information to be measured / detected is not limited, and examples thereof include optical physical properties, electrical physical properties, and magnetic physical properties. By narrowing the arrangement interval of the flow paths in the processing unit 13, for example, when performing detection and measurement by scanning a light spot on a plurality of flow paths, it is possible to arrange the flow paths at a higher density. Yes, desired optical properties can be measured at higher speed and higher density.

  For measuring optical properties, for example, fluorescence measurement, scattered light measurement, transmitted light measurement, reflected light measurement, diffracted light measurement, ultraviolet spectroscopic measurement, infrared spectroscopic measurement, Raman spectroscopic measurement, FRET measurement, FISH measurement and other various spectrum measurements Etc. can be used. For example, when performing fluorescence measurement, a fluorescent dye can be used, and the detection accuracy can be further improved by using together fluorescent dyes having different excitation wavelengths. In particular, since a plurality of channels are provided, fluorescent dyes having different excitation wavelengths may be used for each channel.

  As measurement of electrical properties that can be performed in the present invention, for example, a resistance value, a capacitance value (capacitance value), an inductance value, an impedance, a change value of an electric field between electrodes, and the like related to a sample can be measured. For example, an electrical measurement element is formed in the processing unit 13 or the like in the flow channel in the flow channel, and the sample is passed therethrough to obtain electrical property information. As an example, it is possible to arrange an opposing electrode in the processing unit 13 or the like in the flow path, and measure an electrical resistance, an electrical impedance, or the like generated when the sample passes therethrough.

  As the measurement of the magnetic properties that can be performed in the present invention, for example, measurement of magnetization, magnetic field change, magnetic field change, and the like related to a sample can be performed. As such, for example, a sample whose surface is modified with a magnetic material or magnetic beads can be used. Furthermore, magnetic beads or the like may be integrated with a fluorescent dye. For example, it is possible to measure a cell obtained by reacting an antibody or the like with a magnetic bead by passing it through a processing unit 13 or the like in a flow path disposed in a strong magnetic field. For example, it is possible to measure a frequency spectrum that is a direct current component or a high frequency component of a generated magnetic field by passing a sample through opposing magnetic coils. Alternatively, the change in magnetization can be measured by a magnetoresistive element or the like.

  In the main channel 15, a plurality of channels having substantially the same distance between the merging unit 18 and the processing unit 13 are arranged. That is, by setting the distance from the joining portion 18 where the laminar flow is formed to the processing portion 13 for measurement to be substantially equal, the pressure in the flow path, the flow rate of the sample flowing in the flow path, and the processing speed And so on. Thereby, the dispersion | variation in the process conditions of the sample measured with the process part 13 can be prevented.

  In the present invention, at least the flow path length from the merging section 18 to the processing section 13 may be approximately equal distance, but more preferably, the flow path length from the sample introduction section 11 to the merging section 18 is approximately equal distance. Is desirable. It is desirable that the flow path lengths from the sheath liquid supply part 1211 through which the sheath liquid is introduced into the sheath liquid flow path 17 to the merging part 18 are substantially equidistant. Thereby, the formation conditions of the laminar flow in the confluence | merging part 18 of each main flow path 15 can also be made the same. As a result, variations in processing conditions in the processing unit 13 of each main channel 15 can be prevented more accurately.

  Moreover, it is desirable to arrange each joining part 18 on the same circumference centering on the process part 13. FIG. Thereby, the distance of the confluence | merging part 18 and the process part 13 can be made into equal distance and the shortest. By shortening the channel length, the sample can be transported to the processing unit 13 in a short time after being introduced from the sample introduction unit 11. In particular, when measuring fine particles or the like, the longer the flow path length, the more susceptible to the influence. Therefore, the influence can be eliminated by shortening the flow path length.

  The flow path length, flow path width, flow path depth, etc. of the processing unit 13 are not limited, and can be set to a suitable length, width length, or depth depending on the purpose, but the flow path length of the processing unit 15 is It is desirable that the length is sufficiently shorter than the upstream main channel 15 and the downstream channel 16.

  The sample that has passed through the processing unit 13 is transported further downstream, and the sample and the sheath liquid are discharged in the discharge unit 14. Then, if necessary, the sample (and the sheath liquid) may be collected or collected by the discharge unit 14.

  When the sample taken out from the discharge unit 14 is again subjected to some kind of processing such as sorting and collection, the distance between the processing unit 13 and the discharge unit 14 in each flow path 16 is also approximately equal in each flow path. It is desirable that Thereby, it can sort on the same conditions with the discharge part 14 in each flow path, or it can connect to a subsequent flow path. The case of further transport to the subsequent flow path will be described later.

  FIG. 2 is a conceptual diagram showing an example in which the flow channel structure 1 shown in FIG. 1 is connected in series. Reference numerals U1, U2, U3, U4, U5, U6, U7, U8, and U9 in FIG. 2 indicate the flow channel structures in FIG. In other words, FIG. 2 shows a state in which the next main channel 15 follows the channel 16 of the channel structure 1 of FIG.

  In this way, the next channel structure 1 may be connected in series with the channel structure 1 as a repeating unit. For example, when the main flow path 15 of the next flow path structure U2 continues to the flow path 16 (not shown) of the flow path structure U1, the second processing is performed in the processing unit 13 (not shown) of the flow path structure U2. It can be performed. In this way, the sample can be taken out from the discharge portion Outlet 1 by repeating the flow path structures U3, U4, and U5.

  Similarly, the flow path structure U1 can be branched to different flow path structures U5, U6, U7, U8, and U9. The sample can be taken out from the discharge part Outlet 2 through the flow path composition U9. Then, as shown in FIG. 2, two Inlets 1 and 2 can be provided as sample introduction portions. FIG. 2 illustrates the case where two sample introduction portions Inlet 1 and 2 are provided, but the number is not limited to two, and a desired number of sample introduction portions may be provided as appropriate. The same applies to the discharge unit Outlet. Further, the necessary number of flow path structural units can be connected as appropriate.

  In the present invention, even if a plurality of flow path structures U1 to U9 including the processing unit 13 are arranged, conditions such as pressure and flow velocity in the flow path can be equalized, which is preferable. This enables accurate measurement.

  FIG. 3 is a conceptual diagram of the second embodiment of the flow channel structure according to the present invention. FIG. 4 is a partially enlarged view of the same embodiment. FIG. 5 is a partial perspective view of the embodiment. FIG. 6 is a conceptual diagram for explaining an example of fluid control according to the embodiment. Hereinafter, the difference from the first embodiment will be mainly described, and the description of the common parts will be omitted.

The code | symbol 2 shown in FIG. 3 has shown the flow-path structure based on this invention. The flow channel structure 2 includes a sample introduction part 21, a first sheath liquid introduction part 22, second sheath liquid introduction parts 23 and 23, a processing part 24, and a discharge part 25. The flow path structure 2 includes ten main flow paths 26a, 26b, 26c, 26d, 26e, 26f, 26g, 26h, 26i, and 26j (hereinafter, may be collectively referred to as the main flow path 26) and two references. Channels 28 and 28 are provided.
The enlarged region in FIG. 1 is a region in which a part of the flow path 26j is enlarged.

  In this channel structure 2, the first sheath liquid and the second sheath liquid are used. One feature is that the sample introduction part 21, the first sheath liquid introduction part 22, and the second sheath liquid introduction part 23 are shared by the main flow paths 26a to 26j.

Here, the flow channel structure in one main flow channel 26 will be described with reference to FIGS.
The sample introduction unit 21 communicates with each main channel 26 in each sample supply unit 2111 via the introduction channel 211. The sample supply unit 2111 can supply the sample injected into the sample introduction unit 21 to the main channel 26. Thereby, it is not necessary to provide a sample introduction port in each of the sample supply units 2111.
The first sheath liquid introduction part 22 communicates with the first sheath liquid flow paths 2212 and 2212 in each first sheath liquid supply part 2211 via the introduction flow path 221. The first sheath liquid supply part 2211 can supply the first sheath liquid injected into the first sheath liquid introduction part 22 to the first sheath liquid flow paths 2212 and 2212. This eliminates the need to provide a first sheath liquid inlet in each of the first sheath liquid supply units 2211.
The second sheath liquid introduction part 23 communicates with each of the second sheath liquid flow paths 2312 and 2312 in each second sheath liquid supply part 2311 via the introduction flow path 231. The second sheath liquid supply unit 2311 can supply the second sheath liquid injected into the second sample introduction unit 23 to the second sheath liquid channels 2312 and 2312. This eliminates the need to provide a second sheath liquid inlet in each of the second sheath liquid supply portions 2311.

  The sample is supplied from each sample supply unit 2111 to each main channel 26 from the sample introduction unit 21 via the introduction channel 211. Then, the first sheath liquid flows from the first sheath liquid introduction part 22 via the introduction flow path 221 to the respective first sheath liquid flow paths 2112 and 2112 from the respective first sheath liquid supply parts 2111. And the first sheath liquid is introduced so as to be sandwiched between samples transported in the main flow path 26 by the first junction 261.

  Subsequently, the second sheath liquid flows from each second sheath liquid supply section 2311 to each second sheath liquid flow path 2312 via the introduction flow path 231 from the second sheath liquid introduction section 23. 2312 and the second sheath liquid is introduced so as to be sandwiched between the samples conveyed in the main flow path 26 by the second junction 262.

  As described above, the first sheath liquid is introduced into the sample transported in the main flow path 26 by the first joining section 261, and then the second sheath liquid is introduced by the second joining section 262. By doing so, a laminar flow can be formed more accurately. In this case, as shown in FIG. 5, it is preferable that the flow path structure forms a laminar flow by introducing the second sheath liquid from a direction different from the direction in which the first sheath liquid is introduced. After the sample is sandwiched from the predetermined direction using the first sheath liquid, the sample is sandwiched from the direction different from the predetermined direction using the second sheath liquid, so that the center of the flow path can be more accurately obtained. The sample can be positioned.

  In FIG. 5, the following flow path structure is adopted as the second sheath liquid being introduced from a direction different from the direction in which the first sheath liquid is introduced. If the transport direction of the sample after introducing the first sheath liquid in the first confluence portion 261 with respect to the sample transported from the sample supply unit 2111 is the X-axis direction, the sample is transported at least in the Z-axis direction. Then, the sample is rotated around the Y axis by a predetermined angle (see reference C in FIG. 5), and the second sheath liquid is introduced at the second merging portion 262, so that the sample is focused on the central portion of the main channel 26. Yes. As a result, a laminar flow in which a sample exists only at the center of the flow path can be realized with high accuracy.

  Regarding the formation of laminar flow, it is desirable that the flow path structure is such that the sample is transported substantially perpendicular to the Z-axis direction and rotated substantially perpendicularly around the Y-axis as shown in FIG. It is not limited to. That is, any flow channel structure that can form a laminar flow by transporting a sample at least in the Z-axis direction and rotating it at least by a predetermined angle around the Y-axis may be used.

  Using the first sheath liquid and the second sheath liquid as in the flow path structure 2 and transporting the sample in the Z-axis direction at the bent portion C as the flow path structure, the sample is further rotated around the Y axis by a predetermined angle. By adopting the structure, a highly accurate laminar flow can be realized in the main channel 26. At this time, in the plurality of flow paths 26a to 26j, at least the distance from the second merging section 262 to the processing section 24 is made substantially equal, thereby causing variations in pressure in the main flow path 26 due to variations in flow path length. In addition, variations in the flow rate of the sample can be suppressed. As a result, variations in the processing conditions of the flow paths 26a to 26j in the processing unit 24 can be suppressed. That is, by equalizing the distance from the second merging section 262 to the processing section 24, the sample can be processed with high accuracy and efficiency in the processing section 24 of each main channel 26.

  Furthermore, in the present invention, the first confluence portion where the first sheath fluid is supplied to the sample from the first sheath fluid supply portion 2211 that supplies the first sheath fluid to each first sheath fluid flow path 2212. It is desirable that the distance to H.261 is the same. In addition, the distance from the second sheath liquid supply unit 2311 that supplies the second sheath liquid to each second sheath liquid channel 2312 to the second confluence unit 262 that supplies the second sheath liquid to the sample It is desirable to do the same. In this way, by making the lengths of the respective flow paths until the first sheath liquid and the second sheath liquid are introduced into the sample, the variation in the formation of laminar flow in each main flow path 26 can be eliminated. As a result, variation in the laminar flow state in each main flow path 26 can be prevented, so that each sample can be processed with high accuracy and efficiency.

  Furthermore, since the number of the sample introduction parts 21, the first sheath liquid introduction parts 22, and the second sheath liquid introduction parts 23 can be reduced, the design restrictions as the channel structure can be eased. As a result, since the flow channel structure can be made compact, it can be integrated and contribute to space saving as a device.

  The sample into which the first sheath liquid and the second sheath liquid have been introduced in this way is subjected to predetermined processing such as various measurements and detections by the processing unit 24, and is then discharged through the flow path 27. It is conveyed to 25. In the flow path structure 2, since the discharge part 25 is also shared, the flow paths 27 are arranged substantially in parallel. However, the present invention is not limited to the structure and arrangement of the flow paths 27. Further, in the case where the next process is performed subsequently, it is desirable that the flow path length of the flow path 27 is substantially equal.

  In the present invention, the reference channels 28 can be provided among the plurality of channels. Reference information such as a background can be obtained by flowing a reference substance from the introduction unit 281 into the reference channel 28 and performing the same processing as the main channel 26 by the processing unit 24. Then, the reference material can be discharged / collected from the discharge unit 282.

  For example, when measurement is performed by the processing unit 24, the measurement result of the sample can be corrected based on the reference information obtained from the reference channel 28. As a result, measurement with higher accuracy becomes possible.

  For example, when optical measurement is performed, irradiation is performed while scanning light toward the processing unit 24. In this case, it is desirable to provide the reference channels 28 and 28 at both ends of the plurality of channels.

  As described above, according to the flow path structure according to the present invention, by making the lengths of the plurality of main flow paths 26 equal, variations in pressure, flow velocity, processing conditions, and the like in the flow path due to the flow path lengths are achieved. Can be eliminated. In the flow channel structure having such characteristics, simple and accurate fluid control is possible only by changing conditions such as each flow rate, flow channel width, and flow channel depth. Hereinafter, a description will be given with reference to FIG.

  FIG. 6 is a partially enlarged view of the flow channel structure 2.

  Let Q1 be the flow rate of the sample introduced from the sample supply unit 2111. The flow rates of the first sheath liquid channels 2212 and 2212 are Q2 and Q3. Let Q4 be the flow rate of the sample into which the first sheath liquid is introduced in the first junction 261. The flow rates of the second sheath liquid channels 2312 and 2312 are Q5 and Q6. Let Q7 be the flow rate of the sample into which the second sheath liquid is introduced in the second junction 262 (see FIG. 6).

In this case, the flow rates Q4 and Q7 are expressed by the following formulas (1) and (2).
If the flow path width and the flow path height of the flow path are both equal to W1, the cross-sectional width W2 of the sample with respect to the flow path width W1 when the flow path is viewed in cross section is expressed by the following formula (3). The Similarly, the cross-sectional height W3 of the sample with respect to the flow path height W1 is represented by the following formula (4).

  In this case, if the state in which the laminar flow is formed is W2 = W3, the following equation (6) is obtained.

  That is, in the flow channel structure of the present invention, the flow rate Q1 of the sample, the flow rate Q2 of the first sheath liquid, and the flow rate Q5 of the second sheath liquid are highly accurate by satisfying the relationship of the above formula (6). Laminar flow can be obtained. The formation of the laminar flow can be controlled with high accuracy by controlling the flow rate, the channel width, the channel height, and the like based on the relational expression such as the above formula (6).

  In each main flow path 26 of the flow path structure 2 according to the present invention, the flow path length from the first merge section 261 to the processing section 24 and the flow from the first sheath liquid supply section 2211 to the first merge section 261 are described. By making the path length and the flow path length from the second sheath liquid supply part 2311 to the second merge part 262 equal to each other, at least one of the sample, the first sheath liquid, and the second sheath liquid is used. By controlling the flow rate, an accurate laminar flow can be obtained. The laminar flow can also be controlled by controlling the width and depth of each flow path. As a result, it is possible to control the fluid with high accuracy while being simple.

  FIG. 7 is a conceptual diagram of an FCM apparatus using the flow path substrate of the present invention. The code | symbol D of FIG. 7 has shown the FCM (flow cytometry) apparatus. In this FCM apparatus D, the sample in the flow path is irradiated with light as an optical detection system.

  The sample in the channel substrate A is transported through the central portion in the channel while being sandwiched between fluids. A sample flow including a sample to be measured and a sheath flow are injected into the flow channel in the flow channel substrate A at a specified pressure (flow rate), thereby forming a flow in which cells are aligned. Then, the excitation light L1 is emitted from the light source D5, and is irradiated onto the sample being conveyed while aligning the flow paths in the flow path substrate A through the condenser lens D6.

  When this sample is irradiated with the excitation light L1, fluorescence, forward scattered light (FCS), or the like is generated. Specific wavelengths of the return light L2 are separated by dichroic mirrors D7 and D7 provided on the coaxial optical path and bandpass filters D8, D8, and D8. And it can detect with detector D9 (for example, photo multiplier tube; PMT) for every corresponding wavelength. Thereby, the spectral analysis of the sample in the channel can be performed.

  Furthermore, although not shown in the figure, when a desired sample is obtained according to the analysis result, it is possible to collect only desired cells in a branch region downstream of the flow path. As a sorting method, various sorting methods using a piezoelectric element or an electromagnetic valve can be adopted. Here, the case where a preparative laser is used will be described as an example.

  A preparative laser is separately irradiated at an optimal timing and irradiation power based on the acquired information (for example, fluorescence spectrum, size, speed, etc.) of the spectroscopic detector. And a bubble is produced | generated by the light energy irradiated in the flow path. And the flow change in a flow path arises by generation | occurrence | production of a bubble, Only a desired sample can be guide | induced to the target collection area.

  In this way, in the FCM apparatus D, the sample cells are spectrally analyzed with laser light to determine whether or not the cells are desired, and only the desired cells are sorted in the branch channel (see reference numeral 41). You can also Even with such a branched channel structure, according to the present invention, fluid control can be performed with high accuracy (see, for example, FIGS. 3 and 4).

  Further, even when the distance between the detection system such as the FCM apparatus D and the sorting system is somewhat apart, in order to specify the position of the sample to be collected from the samples transported to the sorting unit, It is important that the sample flow rate is constant. In this regard, in the flow channel structure according to the present invention, the sample can be transported in an orderly manner even in the flow channel. As a result, sample sorting and the like can be performed accurately. Furthermore, since the flow velocity of the sample flowing in the flow path and the position in the flow path are stable, stable spectroscopic analysis and sorting work can be performed.

  Here, the FCM apparatus has been described as an example of application to the measurement apparatus among the processing apparatuses, but the present invention is also applicable to an analysis chip in general that requires control of the position and speed of the sample to be processed. The invention can be used effectively. Applicable devices include, for example, various DNA analyzers, mass spectrometers, and other real-time cell observation devices. Further, it can be applied to various analyzer devices and microreactor devices other than these.

  FIG. 8 is a conceptual diagram for explaining an example of the manufacturing method of the flow path substrate according to the present invention. Here, an example of manufacturing the flow path substrate A provided with the flow path structure 2 will be described. The substrate according to the present invention can be easily manufactured by injection molding using a double-sided mold, mechanical processing using a micro drill, or the like. The flow path substrate A provided with the flow path structure 2 can be obtained from three layers of the substrates A1, A2, and A3.

  The substrate A1 is a first layer substrate, and on the upper surface of the substrate, the sample supply unit 2111, the main channel 26 to the first merge unit 261, the first sheath liquid supply unit 2211, and the first sheath liquid are provided. Grooves respectively corresponding to the flow path 2212 and the second sheath liquid supply unit 2311 are formed.

The substrate A2 is a substrate of the second layer, and on the lower surface of the substrate (bonding surface with the substrate A1), the processing unit 24, the channel 27, the main channel 26 downstream from the first junction 261, and the second Grooves corresponding to the sheath liquid flow paths 2312 and the like are formed.
Furthermore, introduction flow paths 211, 221, and 231 are formed on the upper surface of the substrate A2.

  The substrate A3 is a third layer substrate, and penetrates the substrate A3 to form the sample introduction part 21, the first sheath liquid introduction part 22, the second sheath liquid introduction part 23, the discharge part 25, and the like. Has been.

  With the substrate A1 as the lowest layer, the substrate A2 is laminated on the upper surface of the substrate A1, and the substrate A3 is laminated on the upper surface of the substrate A2, whereby the substrate having the flow path structure 2 can be obtained.

  About manufacture of board | substrate A1, A2, A3, it can manufacture by a well-known method. For example, for the manufacture of the substrate A2, although not shown, a method of setting a top surface mold and a bottom surface mold having a flow path shape and a through hole shape in an injection molding machine and transferring the shape to the substrate A1 is adopted. it can. As a result, the flow path structure and the through-hole shape are formed in the substrate A1 which is injection-molded.

  In addition, a conventional method can be appropriately used as a method for bonding the substrates A1, A2, and A3. As the bonding, for example, heat fusion, adhesive, anodic bonding, bonding using an adhesive sheet, plasma activated bonding, ultrasonic bonding, or the like can be used as appropriate. A suitable bonding method can be selected in consideration of the material, shape, size, etc. of the substrate.

  Furthermore, although not shown in the drawing, it is possible to appropriately include a step of performing surface processing on the surfaces of the substrates A1, A2, and A3 after the injection molding. Thereby, it is possible to control physical properties such as the hydrophobicity of the channel surface.

  In addition, as a manufacturing method of a board | substrate, it is not limited to what is called double-sided shaping | molding, Techniques, such as single-sided shaping | molding, are also employable. As a method of single-sided molding, a conventional method such as so-called plate punching can be used as appropriate, but double-sided molding is desirable from the viewpoint of molding accuracy and the like. Thus, if the substrate adopts the flow channel structure according to the present invention, a flow channel substrate capable of highly accurate fluid control can be manufactured by a simple method such as injection molding using a double-sided mold.

  In particular, the flow path substrate of the present invention can be easily manufactured by injection molding using a double-sided mold and a cover sheet bonding process. Of course, the flow path substrate of the present invention can be easily manufactured even in the injection molding and substrate bonding process using a single-sided mold. Therefore, a flow path substrate capable of highly accurate fluid control can be manufactured at a low manufacturing cost. Thus, the flow channel structure and the flow channel substrate according to the present invention also have manufacturing advantages.

  And when manufacturing the flow-path board | substrate based on this invention, about the material and method used for injection molding, a suitable material and method can be selected suitably. As the substrate, moldable resins can be used, and the type thereof is not limited. For example, a thermoplastic resin can be used. Specific examples include polymethyl methacrylate and silicon resin. When the spectroscopic analysis is performed on the flow path substrate, it is desirable to use a light transmissive resin. In addition, an injection-molded substrate using a low-melting glass, a nanoimprint technique using an ultraviolet curable resin, or the like can be used.

It is a conceptual diagram of 1st Embodiment of the flow-path structure concerning this invention. It is a conceptual diagram which shows an example which connected the flow-path structure 1 shown in FIG. 1 in series. It is a conceptual diagram of 2nd Embodiment of the flow-path structure concerning this invention. It is a partially expanded view of the same embodiment. It is a partial perspective view of the same embodiment. It is a conceptual diagram for demonstrating an example of the fluid control of the embodiment. It is a conceptual diagram with which it uses for description of an example of the manufacturing method of the flow-path board | substrate which concerns on this invention. It is a conceptual diagram of the FCM apparatus using the flow-path board | substrate of this invention. It is a conceptual diagram with which it uses for description of the prior art regarding a flow-path structure.

Explanation of symbols

1, 2 Channel structure 11, 21 Sample introduction unit 12 Sheath liquid introduction unit 13, 24 Processing unit 14, 25 Discharge unit 15, 26 Main channel 17 Sheath liquid channel 18 Merging unit 22 First sheath liquid introduction unit 23 2 sheath liquid introduction part 261 1st junction part 262 2nd junction part A Flow path substrate

Claims (7)

A flow path structure including a plurality of flow paths including at least a sample introduction section for introducing a sample, a processing section for processing the sample, and a discharge section for discharging the sample;
The flow path includes at least a sheath liquid introduction part for introducing a sheath liquid into the sample introduced from the sample introduction part,
A flow path structure in which the distance from the merging portion between the flow path and the sheath liquid introduction section to the processing section is substantially equal in each flow path.   2. The flow channel structure according to claim 1, wherein at least two of the flow channels have the sample introduced into each of the flow channels from the same sample introduction unit.   The flow channel structure according to claim 2, wherein the sheath liquid is introduced into each of the flow paths from the same sheath liquid introduction section. The sheath liquid introduction part of the flow path is
A first sheath liquid introduction section for introducing a first sheath liquid into the sample introduced from the sample introduction section;
A second sheath liquid introduction section for introducing a second sheath liquid from a direction different from the introduction direction of the first sheath liquid to the sample into which the first sheath liquid has been introduced;
Comprising at least
The flow path structure according to claim 1, wherein the distance from the confluence part of the flow path and the second sheath liquid introduction part to the processing part is substantially equal in each flow path. A flow path structure including a plurality of flow paths including at least a sample introduction section for introducing a sample, a processing section for processing the sample, and a discharge section for discharging the sample;
A channel structure in which the distance from the sample introduction unit to the processing unit is substantially equal in each channel. A flow path substrate having a plurality of flow paths each including a sample introduction part for introducing a sample, a processing part for processing the sample, and a discharge part for discharging the sample;
The flow path includes a sheath liquid introduction part that introduces a sheath liquid into the sample introduced from the sample introduction part,
A flow path substrate in which the distance from the joining part of the flow path and the sheath liquid introduction part to the processing part is substantially equal in each flow path.   2. The flow channel structure according to claim 1, wherein at least one of a width and / or depth of the flow channel, a width and / or depth of the sheath liquid introduction portion, a flow rate of the sample, and a flow rate of the sheath liquid is set. A fluid control method that at least controls the position of the sample in the flow path by adjusting.

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