ABSTRACT
Abstract
There is provided a microparticle sorting method including a procedure of collecting a microparticle in a fluid that flows through a main channel in a branch channel that is in communication with the main channel by generating a negative pressure in the branch channel. In the procedure, a flow of a fluid is formed that flows toward a side of the main channel from a side of the branch channel at a communication opening between the main channel and the branch channel.
Description
CROSS REFERENCE TO RELATED APPLICATION
The present application is a continuation application of U.S. patent application Ser. No. 15/658,693, filed Jul. 25, 2017, which is divisional application of U.S. patent application Ser. No. 13/963,188, filed Aug. 9, 2013, now U.S. Pat. No. 9,737,912, which claims the priority from prior Japanese Priority Patent Application JP 2012-180317 filed in the Japan Patent Office on Aug. 16, 2012, the entire content of which is hereby incorporated by reference.
BACKGROUND
The present technology relates to a microparticle sorting method. More specifically, the present technology relates to a microparticle sorting method that separates and recovers only target microparticles from the microparticles that are flowing along a channel.
A microparticle sorting apparatus that forms a microparticle-containing sheath flow in a channel, detects fluorescence and scattered light emitted from the microparticles by irradiating light on the microparticles in the sheath flow, and separates and recovers a microparticle group (population) that exhibits a predetermined optical characteristic is known. For example, in a flow cytometer, a specific type of cell only is separated and recovered by labeling a plurality of types of cell included in a sample with a fluorescent dye and optically identifying the fluorescent dye labeled on each cell.
In JP 2009-100698A and JP 2005-538727T, microchip-type microparticle sorting apparatuses are disclosed that perform analysis by forming a sheath flow in a channel formed on a microchip that is made from plastic, glass or the like.
The microparticle sorting apparatus disclosed in JP 2009-100698A controls the feeding direction of the sheath flow at a branching portion between an introduction channel in which the sheath flow is formed and a branch channel in communication with the introduction channel by generating an air bubble based on laser irradiation at the branching portion. According to this microparticle sorting apparatus, controlling the feeding direction of the sheath flow at the branching portion with an air bubble enables just the target microparticles to be collected into the branch channel from the introduction channel and sorted.
Further, the microfluidic system disclosed in JP 2005-538727T sorts target microparticles by using an actuator to control the feeding direction of a sheath flow at a channel branching portion. In this microfluidic system, the actuator changes the feeding direction of the sheath flow by pressing against a chamber that is connected to a branching portion between an introduction channel in which the sheath flow is formed and a branch channel in communication with the introduction channel to push out fluid in the chamber.
SUMMARY
For microchip-type microparticle sorting apparatuses, in order to further increase the speed and accuracy of analysis, there is a demand for a technology for rapidly and stably extracting only target microparticles from a sheath flow that is flowing through a channel.
According to an embodiment of the present technology, there is provided a microparticle sorting technology that can rapidly and stably extract only target microparticles from a sheath flow that is flowing through a channel.
According to an embodiment of the present technology, there is provided a microparticle sorting method including a procedure of collecting a microparticle in a fluid that flows through a main channel in a branch channel that is in communication with the main channel by generating a negative pressure in the branch channel. In the procedure, a flow of a fluid is formed that flows toward a side of the main channel from a side of the branch channel at a communication opening between the main channel and the branch channel. The flow may be formed by introducing the fluid into the branch channel from an introduction opening positioned near the communication opening in the branch channel. The fluid introduced from the introduction opening into the branch channel is split into a counter flow that flows toward the communication opening and a forward flow that flows in the opposite direction.
In this microparticle sorting method, by maintaining the flow of the fluid formed in the communication opening that flows toward the main channel side from the branch channel side before and after the above-described steps, the fluid in the main channel can be prevented from unnecessarily entering the branch channel during the period that a negative pressure is not being generated in the branch channel.
According to the microparticle sorting method of the present technology, in the procedure, a flow rate of the fluid that is sucked into the branch channel from the main channel due to negative pressure may be greater than a flow rate of the fluid introduced into the branch channel from the introduction opening and fed toward the communication opening. The microparticle in the main channel may be hereby collected from the communication opening to a position that is past the introduction opening of the branch channel.
According to the microparticle sorting method of the present technology, in the procedure, the negative pressure may be generated by an actuator applying a force that deforms an inner space of the branch channel to cause a volume of the inner space to increase
A change in the negative pressure may have a pulse waveform, a step waveform, or an undershoot-step waveform.
According to an embodiment of the present technology, there is provided a microchip for sorting microparticles, including a sample fluid introduction opening into which a sample fluid including a microparticle is introduced, a sample fluid channel through which the sample fluid introduced from the sample fluid introduction opening flows, a sheath fluid introduction opening into which a sheath fluid is introduced, a first sheath fluid channel through which the sheath fluid introduced from the sheath fluid introduction opening flows, a main channel where the sample fluid channel and the first sheath fluid channel merge, a branch channel that is in communication with the main channel, and a second sheath fluid channel that connects the sheath fluid introduction opening and a sheath fluid discharge opening that is positioned near a communication opening to the main channel in the branch channel, and that feeds the sheath fluid introduced from the sheath fluid introduction opening into the branch channel from the sheath fluid discharge opening. According to the microchip for sorting microparticles of the present technology, the second sheath fluid channel may not be in communication with the sample fluid channel, the first sheath fluid channel, or the main channel. An actuator for applying a displacement on a contact surface may be arranged in contact with a position corresponding to the branch channel on a surface. A pressure chamber for producing a change in volume due to the displacement may be configured in the branch channel. The communication opening, the sheath fluid discharge opening, and the pressure chamber may be arranged in the branch channel in order of mention. The microchip for sorting microparticles may further include the two first sheath fluid channels. The sheath fluid introduction opening may be provided at a symmetrical center of the two first sheath fluid channels. An end on an opposite side to the communication opening of the branch channel may be an open end.
In an embodiment of the present technology, the term âmicroparticleâ has a broad meaning that includes biologically-relevant microparticles such as cells, microbes, ribosomes and the like, as well as synthetic particles such as latex particles, gel particles, industrial particles and the like.
Examples of biologically-relevant microparticles include the chromosomes, liposomes, mitochondria, organelles (cell organelles) that form various cells. Examples of cells include animal cells (hematopoietic cells etc.) and plant cells. Examples of microbes include bacteria such as E. coli , viruses such as tobacco mosaic virus, fungi such as yeast and the like. Further example of biologically-relevant microparticles includes nucleic acids, proteins, complexes of these and the like. Examples of industrial particles include organic or inorganic polymer materials, metals and the like. Examples of organic polymer materials include polystyrene, styrene-divinyl benzene, poly methyl methacrylate and the like. Examples of inorganic polymer materials include glass, silica, magnetic materials and the like. Examples of metals include metal colloids, aluminum and the like. Although the shape of these microparticles is usually spherical, the microparticles may also have a non-spherical shape. Further, the size and mass of these microparticles is not especially limited.
According to the embodiments of the present technology described above, a microparticle sorting technology is provided that can rapidly and stably extract only target microparticles from a sheath flow that is flowing through a channel.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram illustrating a configuration of a microparticle sorting apparatus A according to a first embodiment of the present technology;
FIG. 2 is a diagram illustrating a configuration of a microchip 1 a that is mounted on a microparticle sorting apparatus A;
FIG. 3 is a diagram illustrating a configuration of the microchip 1 a;
FIG. 4 is a diagram illustrating a configuration of the microchip 1 a;
FIGS. 5A, 5B and 5C are diagrams illustrating a configuration of a branching portion between a main channel 15 and a sorting channel 16 of the microchip 1 a;
FIG. 6 is a diagram illustrating a configuration of a sheath fluid inlet 13 side end of a sheath fluid bypass channel 18 of the microchip 1 a;
FIG. 7 is a diagram illustrating a configuration of a discharge opening 181 side end of the sheath fluid bypass channel 18 of the microchip 1 a;
FIGS. 8A, 8B, 8C, 8D, 8E and 8F are diagrams illustrating a sorting operation in the microparticle sorting apparatus A;
FIGS. 9A and 9B are diagrams illustrating functions of a pressure chamber 161 in the microchip 1 a;
FIG. 10 is a diagram illustrating a configuration of a modified example of the microchip 1 a;
FIG. 11 is a diagram illustrating a flow of a sample fluid and a sheath fluid that may be produced at a branching portion between the main channel 15 and the sorting channel 16 ;
FIGS. 12A and 12B are diagrams illustrating a flow of the sheath fluid introduced from the discharge opening 181 of the sorting channel 16 ;
FIGS. 13A and 13B are diagrams illustrating a position where a target particle is drawn in during a sorting operation;
FIGS. 14A, 14B and 14C are diagrams illustrating waveforms of the voltage applied on an actuator 31 from a drive unit 23 ; and
FIG. 15 is a diagram illustrating a configuration of a modified example of the microchip 1 a.
DETAILED DESCRIPTION OF THE EMBODIMENT(S)
Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the appended drawings. Note that, in this specification and the appended drawings, structural elements that have substantially the same function and structure are denoted with the same reference numerals, and repeated explanation of these structural elements is omitted. The description will be made in the following order.
1. Microparticle sorting apparatus and microchip for microparticle sorting that are capable of implementing the microparticle sorting method according to an embodiment of the present technology
(Overall configuration of the apparatus)
(Microchip configuration)
2. Microparticle sorting method according to an embodiment of the present technology
(Sorting operation)
(Counter Flow)
(Drive signal)
3. Modified example of the microparticle sorting method according to an embodiment of the present technology
4. Microparticle sorting program
1. Microparticle Sorting Apparatus and Microchip for Microparticle Sorting that are Capable of Implementing the Microparticle Sorting Method According to an Embodiment of the Present Technology
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CROSS REFERENCE TO RELATED APPLICATION
The present application is a continuation application of U.S. patent application Ser. No. 15/658,693, filed Jul. 25, 2017, which is divisional application of U.S. patent application Ser. No. 13/963,188, filed Aug. 9, 2013, now U.S. Pat. No. 9,737,912, which claims the priority from prior Japanese Priority Patent Application JP 2012-180317 filed in the Japan Patent Office on Aug. 16, 2012, the entire content of which is hereby incorporated by reference.
BACKGROUND
The present technology relates to a microparticle sorting method. More specifically, the present technology relates to a microparticle sorting method that separates and recovers only target microparticles from the microparticles that are flowing along a channel.
A microparticle sorting apparatus that forms a microparticle-containing sheath flow in a channel, detects fluorescence and scattered light emitted from the microparticles by irradiating light on the microparticles in the sheath flow, and separates and recovers a microparticle group (population) that exhibits a predetermined optical characteristic is known. For example, in a flow cytometer, a specific type of cell only is separated and recovered by labeling a plurality of types of cell included in a sample with a fluorescent dye and optically identifying the fluorescent dye labeled on each cell.
In JP 2009-100698A and JP 2005-538727T, microchip-type microparticle sorting apparatuses are disclosed that perform analysis by forming a sheath flow in a channel formed on a microchip that is made from plastic, glass or the like.
The microparticle sorting apparatus disclosed in JP 2009-100698A controls the feeding direction of the sheath flow at a branching portion between an introduction channel in which the sheath flow is formed and a branch channel in communication with the introduction channel by generating an air bubble based on laser irradiation at the branching portion. According to this microparticle sorting apparatus, controlling the feeding direction of the sheath flow at the branching portion with an air bubble enables just the target microparticles to be collected into the branch channel from the introduction channel and sorted.
Further, the microfluidic system disclosed in JP 2005-538727T sorts target microparticles by using an actuator to control the feeding direction of a sheath flow at a channel branching portion. In this microfluidic system, the actuator changes the feeding direction of the sheath flow by pressing against a chamber that is connected to a branching portion between an introduction channel in which the sheath flow is formed and a branch channel in communication with the introduction channel to push out fluid in the chamber.
SUMMARY
For microchip-type microparticle sorting apparatuses, in order to further increase the speed and accuracy of analysis, there is a demand for a technology for rapidly and stably extracting only target microparticles from a sheath flow that is flowing through a channel.
According to an embodiment of the present technology, there is provided a microparticle sorting technology that can rapidly and stably extract only target microparticles from a sheath flow that is flowing through a channel.
According to an embodiment of the present technology, there is provided a microparticle sorting method including a procedure of collecting a microparticle in a fluid that flows through a main channel in a branch channel that is in communication with the main channel by generating a negative pressure in the branch channel. In the procedure, a flow of a fluid is formed that flows toward a side of the main channel from a side of the branch channel at a communication opening between the main channel and the branch channel. The flow may be formed by introducing the fluid into the branch channel from an introduction opening positioned near the communication opening in the branch channel. The fluid introduced from the introduction opening into the branch channel is split into a counter flow that flows toward the communication opening and a forward flow that flows in the opposite direction.
In this microparticle sorting method, by maintaining the flow of the fluid formed in the communication opening that flows toward the main channel side from the branch channel side before and after the above-described steps, the fluid in the main channel can be prevented from unnecessarily entering the branch channel during the period that a negative pressure is not being generated in the branch channel.
According to the microparticle sorting method of the present technology, in the procedure, a flow rate of the fluid that is sucked into the branch channel from the main channel due to negative pressure may be greater than a flow rate of the fluid introduced into the branch channel from the introduction opening and fed toward the communication opening. The microparticle in the main channel may be hereby collected from the communication opening to a position that is past the introduction opening of the branch channel.
According to the microparticle sorting method of the present technology, in the procedure, the negative pressure may be generated by an actuator applying a force that deforms an inner space of the branch channel to cause a volume of the inner space to increase
A change in the negative pressure may have a pulse waveform, a step waveform, or an undershoot-step waveform.
According to an embodiment of the present technology, there is provided a microchip for sorting microparticles, including a sample fluid introduction opening into which a sample fluid including a microparticle is introduced, a sample fluid channel through which the sample fluid introduced from the sample fluid introduction opening flows, a sheath fluid introduction opening into which a sheath fluid is introduced, a first sheath fluid channel through which the sheath fluid introduced from the sheath fluid introduction opening flows, a main channel where the sample fluid channel and the first sheath fluid channel merge, a branch channel that is in communication with the main channel, and a second sheath fluid channel that connects the sheath fluid introduction opening and a sheath fluid discharge opening that is positioned near a communication opening to the main channel in the branch channel, and that feeds the sheath fluid introduced from the sheath fluid introduction opening into the branch channel from the sheath fluid discharge opening. According to the microchip for sorting microparticles of the present technology, the second sheath fluid channel may not be in communication with the sample fluid channel, the first sheath fluid channel, or the main channel. An actuator for applying a displacement on a contact surface may be arranged in contact with a position corresponding to the branch channel on a surface. A pressure chamber for producing a change in volume due to the displacement may be configured in the branch channel. The communication opening, the sheath fluid discharge opening, and the pressure chamber may be arranged in the branch channel in order of mention. The microchip for sorting microparticles may further include the two first sheath fluid channels. The sheath fluid introduction opening may be provided at a symmetrical center of the two first sheath fluid channels. An end on an opposite side to the communication opening of the branch channel may be an open end.
In an embodiment of the present technology, the term âmicroparticleâ has a broad meaning that includes biologically-relevant microparticles such as cells, microbes, ribosomes and the like, as well as synthetic particles such as latex particles, gel particles, industrial particles and the like.
Examples of biologically-relevant microparticles include the chromosomes, liposomes, mitochondria, organelles (cell organelles) that form various cells. Examples of cells include animal cells (hematopoietic cells etc.) and plant cells. Examples of microbes include bacteria such as E. coli , viruses such as tobacco mosaic virus, fungi such as yeast and the like. Further example of biologically-relevant microparticles includes nucleic acids, proteins, complexes of these and the like. Examples of industrial particles include organic or inorganic polymer materials, metals and the like. Examples of organic polymer materials include polystyrene, styrene-divinyl benzene, poly methyl methacrylate and the like. Examples of inorganic polymer materials include glass, silica, magnetic materials and the like. Examples of metals include metal colloids, aluminum and the like. Although the shape of these microparticles is usually spherical, the microparticles may also have a non-spherical shape. Further, the size and mass of these microparticles is not especially limited.
According to the embodiments of the present technology described above, a microparticle sorting technology is provided that can rapidly and stably extract only target microparticles from a sheath flow that is flowing through a channel.
BRIEF DESCRIPTION OF THE DRAWINGS
FIG. 1 is a diagram illustrating a configuration of a microparticle sorting apparatus A according to a first embodiment of the present technology;
FIG. 2 is a diagram illustrating a configuration of a microchip 1 a that is mounted on a microparticle sorting apparatus A;
FIG. 3 is a diagram illustrating a configuration of the microchip 1 a;
FIG. 4 is a diagram illustrating a configuration of the microchip 1 a;
FIGS. 5A, 5B and 5C are diagrams illustrating a configuration of a branching portion between a main channel 15 and a sorting channel 16 of the microchip 1 a;
FIG. 6 is a diagram illustrating a configuration of a sheath fluid inlet 13 side end of a sheath fluid bypass channel 18 of the microchip 1 a;
FIG. 7 is a diagram illustrating a configuration of a discharge opening 181 side end of the sheath fluid bypass channel 18 of the microchip 1 a;
FIGS. 8A, 8B, 8C, 8D, 8E and 8F are diagrams illustrating a sorting operation in the microparticle sorting apparatus A;
FIGS. 9A and 9B are diagrams illustrating functions of a pressure chamber 161 in the microchip 1 a;
FIG. 10 is a diagram illustrating a configuration of a modified example of the microchip 1 a;
FIG. 11 is a diagram illustrating a flow of a sample fluid and a sheath fluid that may be produced at a branching portion between the main channel 15 and the sorting channel 16 ;
FIGS. 12A and 12B are diagrams illustrating a flow of the sheath fluid introduced from the discharge opening 181 of the sorting channel 16 ;
FIGS. 13A and 13B are diagrams illustrating a position where a target particle is drawn in during a sorting operation;
FIGS. 14A, 14B and 14C are diagrams illustrating waveforms of the voltage applied on an actuator 31 from a drive unit 23 ; and
FIG. 15 is a diagram illustrating a configuration of a modified example of the microchip 1 a.
DETAILED DESCRIPTION OF THE EMBODIMENT(S)
Hereinafter, preferred embodiments of the present disclosure will be described in detail with reference to the appended drawings. Note that, in this specification and the appended drawings, structural elements that have substantially the same function and structure are denoted with the same reference numerals, and repeated explanation of these structural elements is omitted. The description will be made in the following order.
1. Microparticle sorting apparatus and microchip for microparticle sorting that are capable of implementing the microparticle sorting method according to an embodiment of the present technology
(Overall configuration of the apparatus)
(Microchip configuration)
2. Microparticle sorting method according to an embodiment of the present technology
(Sorting operation)
(Counter Flow)
(Drive signal)
3. Modified example of the microparticle sorting method according to an embodiment of the present technology
4. Microparticle sorting program
1. Microparticle Sorting Apparatus and Microchip for Microparticle Sorting that are Capable of Implementing the Microparticle Sorting Method According to an Embodiment of the Present Technology
(Overall Configuration of the Apparatus)
FIG. 1 is a diagram illustrating a configuration of a microparticle sorting apparatus A that is suited to implementing the microparticle sorting method according to an embodiment of the present technology. Further, FIGS. 2 to 4 are diagrams illustrating a configuration of a microchip 1 a that is mounted on the microparticle sorting apparatus A. FIG. 2 is a top view, FIG. 3 is a perspective view, and FIG. 4 is a cross-sectional view along the cross-section Q-Q in FIG. 2 .
The microparticle sorting apparatus A includes a microchip 1 a , an irradiation unit 21 , a detection unit 22 , and a drive unit 23 . On the microchip 1 a is formed a main channel 15 through which a fluid (sample fluid) including microparticles that are the target of analysis (refer to FIG. 2 ). Further, an actuator 31 is arranged on the surface of the microchip 1 a (refer to FIG. 3 ).
The irradiation unit 21 irradiates light (excitation light) on the microparticles flowing through the main channel 15 on the microchip 1 a . The irradiation unit 21 includes, for example, a light source that emits excitation light and an objective lens that focuses the excitation light on the microparticles flowing through the main channel 15 . The light source may be appropriately selected based on the analysis objective from among a laser diode, a SHG laser, a solid laser, a gas laser, a high luminance LED and the like. The irradiation unit 21 can optionally also have optical elements other than the light source and the objective lens.
The detection unit 22 detects fluorescence and scattered light that are emitted from the microparticles due to the irradiation with excitation light. The detection unit 22 includes an objective lens, which focuses the fluorescence and scattered light emitted from the microparticles, a detector and the like. The detection unit 22 may optionally also have optical elements other than the objective lens and the detector.
The fluorescence that is detected by the detection unit 22 may be fluorescence emitted from the microparticles themselves or fluorescence emitted from a fluorescent substance that is labeled on the microparticles. Further, the scattered light that is detected by the detection unit 22 may be various types of scattered light, such as forward scattered light, side scattered light, Rayleigh scattered light, and Mie scattering.
The fluorescence and scattered light detected by the detection unit 22 are converted into an electric signal, and the electric signal is output to the drive unit 23 . The drive unit 23 determines the optical characteristics of the microparticles based on the input electric signal. Further, the drive unit 23 has a function for collecting microparticles that have been determined to satisfy a predetermined characteristic from the main channel 15 in a sorting channel 16 by applying a voltage to the actuator 31 and controlling that voltage. This function of the drive unit 23 will be described in more detail below. The drive unit 23 is configured from a hard disk in which programs and an OS for executing the below-described various processes are stored, a CPU, a memory and the like.
(Microchip Configuration)
The configuration of the microchip 1 a will now be described in more detail with reference to FIGS. 2 to 4 . A sample fluid that includes microparticles is introduced from a sample fluid inlet 11 into a sample fluid channel 12 . Further, a sheath fluid is introduced from a sheath fluid inlet 13 . The sheath fluid introduced from the sheath fluid inlet 13 is split and fed into two sheath fluid channels
14 and 14 . The sample fluid channel 12 and the sheath fluid channels
14 and 14 merge to form the main channel 15 . A sample fluid laminar flow fed through the sample fluid channel 12 and a sheath fluid laminar flow fed through the sheath fluid channels
14 and 14 merge in the main channel 15 , and form a sheath flow in which the sample fluid laminar flow is sandwiched by the sheath fluid laminar flow.
Further, the sheath fluid introduced from the sheath fluid inlet 13 is also fed to a sheath fluid bypass channel 18 that is formed separately to the sheath channel 14 . One end of the sheath fluid bypass channel 18 is connected to the sheath fluid inlet 13 , and the other end is connected in the vicinity of the communication opening to the main channel 15 of a below-described sorting channel 16 (refer to FIG. 4 ). Although the sheath fluid introduction end of the sheath fluid bypass channel 18 may be connected to any site where the sheath fluid is flowing, including the sheath fluid inlet 13 and the sheath fluid channels
14 and 14 , it is preferred that the sheath fluid bypass channel 18 is connected to the sheath fluid inlet 13 . By connecting the sheath fluid bypass channel 18 at a center position (i.e., in the present embodiment, at the sheath fluid inlet 13 ) where the two sheath fluid channels 14 are geometrically symmetrical, equal amounts of the sheath fluid flow can be made to flow to the two sheath fluid channels 14 . Reference numeral 156 in FIG. 4 denotes a communication opening of the sorting channel 16 to the main channel 15 , and reference numeral 181 denotes a discharge opening to the sorting channel 16 of the sheath fluid that is fed through the sheath fluid bypass channel 18 .
Reference numeral 15 a in FIG. 2 denotes a detection area where excitation light is irradiated by the irradiation unit 21 and fluorescence and scattered light are detected by the detection unit 22 . The microparticles are fed to the detection area 15 a in a single line arranged in the sheath flow formed in the main channel 15 , and are irradiated with the excitation light from the irradiation unit 21 .
The main channel 15 splits into three channels downstream from of the detection area 15 a . A configuration of the branching portion of the main channel 15 is illustrated in FIGS. 5A, 5B and 5C . Downstream from the detection area 15 a , the main channel 15 is in communication with three branch channels, the sorting channel 16 and waste channels
17 and 17 . Of these, the sorting channel 16 is a channel into which microparticles that have been determined by the drive unit 23 to satisfy a predetermined optical characteristic (hereinafter referred to as âtarget particlesâ) are collected. On the other hand, microparticles that are determined by the drive unit 23 as not satisfying the predetermined optical characteristic (hereinafter referred to as ânon-target particlesâ) are not collected in the sorting channel 16 , and flow into either of the two waste channels
17 and 17 .
The sheath fluid bypass channel 18 is connected to the discharge opening 181 positioned near the communication opening 156 to the main channel 15 of the sorting channel 16 (refer to FIG. 4 ). The sheath fluid introduced from the sheath fluid inlet 13 is introduced from the discharge opening 181 into the sorting channel 16 , and forms a sheath fluid flow at the communication opening 156 that flows from the sorting channel 16 side toward the main channel 15 side (this flow will be described in more detail blow).
The microchip 1 a is formed from three substrate layers. The sample fluid channel 12 , the sheath flow channel 14 , the main channel 15 , the sorting channel 16 , and the waste channel 17 are formed by a first substrate layer a 1 and a second substrate layer a 2 (refer to FIG. 4 ). On the other hand, the sheath fluid bypass channel 18 is formed by the second substrate layer a 2 and a third substrate layer a 3 . The sheath fluid bypass channel 18 formed by the substrate layers a 2 and a 3 is connected with the sheath fluid inlet 13 and the discharge opening 181 of the sorting channel 16 without being in communication with the sample fluid channel 12 , the sheath channel 14 , or the main channel 15 . The configuration of the sheath fluid inlet 13 side end and of the discharge opening 181 side end of the sheath fluid bypass channel 18 is illustrated in FIGS. 6 and 7 , respectively.
It is noted that the layer configuration of the substrate layers of the microchip 1 a is not limited to three layers. Further, the configuration of the sheath fluid bypass channel 18 is also not limited to that illustrated in the drawings, as long as the sheath fluid bypass channel 18 is connected with the sheath fluid inlet 13 and the discharge opening 181 of the sorting channel 16 without meeting the sample fluid channel 12 , the sheath channel 14 , or the main channel 15 .
The collecting of the target particles into the sorting channel 16 is performed by generating a negative pressure in the sorting channel 16 with the actuator 31 to suck the sample fluid including the target particles and the sheath fluid into the sorting channel 16 . The actuator 31 is a piezo element or similar device. The actuator 31 is arranged in contact with the surface of the microchip 1 a , at a position corresponding to the sorting channel 16 . More specifically, the actuator 31 is arranged at a position corresponding to a pressure chamber 161 that is provided in the sorting channel 16 as an area whose inner space has expanded (refer to FIGS. 3 and 4 ). The pressure chamber 161 is positioned downstream from of the communication opening 156 and the discharge opening 181 in the sorting channel 16 .
The inner space of the pressure chamber 161 is, as illustrated in FIG. 2 , expanded in a planar direction (width direction of the sorting channel 16 ), and as illustrated in FIG. 4 , expanded in a cross-sectional direction (height direction of the sorting channel 16 ). Namely, the sorting channel 16 is expanded in the width direction and in the height direction at the pressure chamber 161 . In other words, the sorting channel 16 is formed so that its vertical cross-section increases in size in the flow direction of the sample fluid and the sheath fluid at the pressure chamber 161 .
The actuator 31 causes the pressure in the sorting channel 16 to change via the surface (contact face) of the microchip 1 a by producing a stretching force due to a change in the applied voltage. When a flow is produced in the sorting channel 16 due to a change in the pressure in the sorting channel 16 , the volume of the sorting channel 16 simultaneously changes too. The volume of the sorting channel 16 changes until it reaches a volume that is stipulated based on the displacement of the actuator 31 corresponding to the applied voltage. More specifically, when a voltage has been applied and the sorting channel 16 is in a stretched state, the actuator 31 keeps the volume of the pressure chamber 161 small by pressing against a displacement plate 311 forming the pressure chamber 161 (refer to FIG. 4 ). When the applied voltage decreases, the actuator 31 generates a force in a contracting direction, whereby the pressing against the displacement plate 311 weakens and a negative pressure is generated in the pressure chamber 161 .
In order to efficiently transmit the stretching force of the actuator 31 into the pressure chamber 161 , as illustrated in FIG. 4 , it is preferred to form a recess on the surface of the microchip 1 a at the position corresponding to the pressure chamber 161 , and arrange the actuator 31 in this recessed portion. Consequently, the displacement plate 311 that serves as the contact face of the actuator 31 can be made thinner, so that the displacement plate 311 can be easily displaced by changes in the pressing force generated by expansion and contraction of the actuator 31 , allowing the volume of the pressure chamber 161 to change.
In FIGS. 4, 5A, 5B and 5C , reference numeral 156 denotes a communication opening of the sorting channel 16 to the main channel 15 . The target particles being fed in the sheath flow formed in the main channel 15 are collected in the sorting channel 16 from the communication opening 156 . To facilitate the collection of the tar
CLAIMS
Claims ( 23 )
What is claimed is:
1. A microchip, comprising:
a first fluid channel through which a first fluid flows, wherein the first fluid comprises of a plurality of microparticles;
a branch channel in communication with the first fluid channel via a first communication opening;
a switching portion communicated with an actuator to generate a pressure to deflect a selected microparticle of the plurality of microparticles into the branch channel; and
a second fluid channel in communication with the branch channel via a second communication opening in the branch channel, wherein
a second fluid flows from the second fluid channel to the second communication opening, and
the second fluid channel is perpendicular to the branch channel.
2. The microchip according to claim 1 , wherein the switching portion is further configured to:
generate a force based on a change in a voltage applied to the actuator; and
change the pressure in the branch channel based on the force.
3. The microchip according to claim 2 , wherein
the actuator is configured to apply a displacement on a surface of the microchip based on the applied voltage, and
the actuator is at a position, corresponding to the branch channel, on the surface of the microchip.
4. The microchip according to claim 1 , wherein
the switching portion comprising a pressure chamber configured to communicate with the branch channel, and
the pressure chamber is configured to produce a change in volume of the branch channel.
5. The microchip according to claim 1 , wherein
the first fluid flows in a first direction, and
at least of a portion of the second fluid flows, in a second direction opposite to the first direction, through the second fluid channel from a side of the branch channel towards a side of the first fluid channel.
6. The microchip according to claim 1 , further comprising two sheath fluid channels configured to introduce sheath fluid flow into the first fluid channel to form a laminar flow.
7. The microchip according to claim 6 , further comprising a first inlet configured to communicate with the first fluid channel, a sheath inlet configured to communicate with the sheath fluid channels, a second inlet configured to communicate with the second fluid channel.
8. The microchip according to claim 7 , wherein the two sheath fluid channels comprise a sheath fluid introduction opening at a symmetrical center of the two sheath fluid channels.
9. The microchip according to claim 1 , further comprising a waste fluid channel configured to communicate with the first fluid channel via the first communication opening.
10. The microchip according to claim 1 , wherein
the actuator is on a surface of the microchip at a position corresponding to a pressure chamber, and
the pressure chamber is in the branch channel.
11. The microchip according to claim 10 , wherein
the surface of the microchip comprises a recess portion at the position corresponding to the pressure chamber, and
the actuator is in the recess portion.
12. The microchip according to claim 1 , wherein the actuator is a piezo element.
13. The microchip according to claim 1 , wherein the second fluid channel is perpendicular to a substrate layer.
14. The microchip according to claim 1 , wherein the second fluid channel is perpendicular to the first fluid channel.
15. The microchip according to claim 1 , wherein
the first fluid channel comprises a first substrate layer and a second substrate layer, and
the second fluid channel comprises a third substrate layer.
16. The microchip according to claim 1 , wherein an area of the switching portion is bigger than an area of the branch channel.
17. The microchip according to claim 1 , further comprising a processor configured to control a voltage of the actuator based on the flow of the second fluid.
18. The microchip according to claim 17 , wherein the processor is further configured to control the flow of the second fluid to prevent at least one non-target microparticle of the plurality of microparticles to enter the branch channel.
19. A microparticle sorting device, comprising
an actuator,
a microchip, comprising:
a first fluid channel through which a first fluid flows, wherein the first fluid comprises a plurality of microparticles;
a branch channel in communication with the first fluid channel via a first communication opening;
a switching portion communicated with the actuator to generate a pressure to deflect a selected microparticle of the plurality of microparticles into the branch channel; and
a second fluid channel in communication with the branch channel via a second communication opening in the branch channel, wherein
a second fluid flows from the second fluid channel to the second communication opening, and
the second fluid channel is perpendicular to the branch channel.
20. The microparticle sorting device according to claim 19 , further comprising:
a light source configured to irradiate light into the plurality of microparticles; and
a detector configured to detect light emitted from the plurality of microparticles, wherein the actuator is on a surface of the microchip.
21. The microparticle sorting device according to claim 20 , further comprising:
circuitry configured to control a voltage applied to the actuator based on the light detected by the detector to generate the pressure.
22. The microparticle sorting device according to claim 21 , wherein the pressure comprises at least one of a pulse waveform, a step waveform, or an undershoot-step waveform.
23. The microparticle sorting device according to claim 19 , wherein the plurality of microparticles are at least one of cells, chromosomes, liposomes, mitochondria, cell organelles, viruses, nucleic acids, proteins, or complexes thereof.
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