WO2017173820A1

WO2017173820A1 - Microchannel structure utilizing single-path sheath fluid for implementing two-dimensional hydrodynamic focusing and microfluidic chip

Info

Publication number: WO2017173820A1
Application number: PCT/CN2016/105081
Authority: WO
Inventors: 尤政; 赵精晶; 李滨
Original assignee: 清华大学
Priority date: 2016-04-06
Filing date: 2016-11-08
Publication date: 2017-10-12
Also published as: CN105854963A; CN105854963B

Abstract

A microchannel structure (100) utilizing a single-path sheath fluid for implementing two-dimensional hydrodynamic focusing, and a microfluidic chip (1) having same. The microchannel structure (100) comprises: a sample stream channel (111); upper level longitudinal focusing stream channels (120), the upper level longitudinal focusing stream channels (120) being stacked above the sample stream channel (111); lower level longitudinal focusing stream channels (130), the lower level longitudinal focusing stream channels (130) being stacked below the sample stream channel (111); two transverse focusing stream channels (112), the two transverse focusing stream channels (112) being provided respectively at the left side or right side of the sample stream channel (111), the width of each transverse focusing stream channel (112) gradually decreasing from the rear to the front in the direction of fluid flow, and the maximum width of each transverse focusing stream channel (112) being greater than the width of the sample stream channel (111).

Description

Microfluidic structure and microfluidic chip for two-dimensional hydrodynamic focusing using a single sheath liquid

Technical field

The present invention relates to the field of microfluidic channel technology, and more particularly to a microfluidic structure that utilizes a single sheath fluid to achieve two-dimensional hydrodynamic focusing and is a microfluidic chip.

Background technique

In combination with flow cytometry, microfluidic chips are often used to detect biological particles such as cells, embryos, RNA, DNA, protein particles, microorganisms, viruses, and the like. In the detection, the microfluidic chip needs to stably focus the sample stream containing the biological particles at the center of the microchannel to improve the accuracy, sensitivity and stability of the detection. Limited by processing technology, microchannels can only achieve complex curved structures in a plane, but in the vertical direction are mostly vertical pipe walls, or inclined or bowl-shaped pipe walls determined by the machining process. Therefore, the microchannel structure in the related art can complete the lateral focusing of the sample stream in the horizontal plane, but it is difficult to complete the vertical focusing in the vertical direction and the two-dimensional focusing in both directions at the same time, and it is difficult to focus the sample stream on the micro. The center of the runner. Some design structures can achieve two-dimensional focusing, but the flow rate is lower, and the sample flow is focused after the cross-sectional area is larger, such as the center flow rate is less than 1m / s, the cross-sectional area side length is tens of microns, and the center of the commercial flow cytometer The flow rate is usually 3-10 m/s, and the size of the biological particles is more than 10 μm or less. Therefore, these designs cannot achieve high-speed detection of biological particles, and at the same time reduce the accuracy and stability of detection. In addition, some micro-channel structures can achieve two-dimensional focusing, and have high flow velocity and small cross-section characteristics.

Summary of the invention

The present invention aims to solve at least one of the technical problems in the related art to some extent. To this end, the present invention proposes a microchannel structure that realizes two-dimensional hydrodynamic focusing using a single sheath liquid, and the microchannel flow structure can realize a two-dimensional focusing function by using a single sheath liquid, and has a simple structure.

The present invention also provides a microfluidic chip having the above-described microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid.

A microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the first aspect of the present invention includes: a sample flow channel extending in a straight line in a front-rear direction, the sample flow Both ends of the flow channel form a sample inflow port and a liquid outflow port; an upper layer longitudinally focusing flow channel, the upper layer longitudinal focusing flow channel is superposed above the sample flow channel and is in communication with the sample flow channel; a lower longitudinal focusing flow channel, the lower longitudinal focusing flow channel is superposed below the sample flow channel and in communication with the sample flow channel; two lateral focusing flow channels, the two lateral focusing Flow channels are respectively disposed at left and right sides of the sample flow channel, and are respectively connected to the sample flow channel, the upper longitudinal focusing flow channel, and the lower longitudinal focusing flow channel, respectively The lateral focusing flow channel is in the direction of the liquid flow, from back to front The width is gradually reduced, and the maximum width of each of the lateral focusing flow channels is greater than the width of the sample flow path.

According to an embodiment of the invention, a microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid is provided, and two lateral focusing flow channels are disposed on the left and right sides of the sample focusing flow channel, so that the sample flow can first achieve lateral direction. Focusing, that is, compressing the size of the sample stream in the lateral direction, and positioning the upper longitudinal focusing flow channel and the lower longitudinal focusing flow channel above and below the lateral focusing flow path at corresponding positions, so that the sample flow can be longitudinally Focusing, that is, when the sheath flow in the upper longitudinal focusing flow channel and the lower longitudinal focusing flow channel symmetrically enters the sample flow channel of the intermediate layer, the longitudinal dimension of the sample flow can be compressed, thereby achieving two-dimensional focusing of the sample flow as a whole. Since the flow rate of the sheath liquid flow is much larger than the flow rate of the sample flow, the width of the lateral focus flow flow path is set to be larger than the width of the sample flow flow path, and the speed/dynamic pressure of the sample flow when the sample flow and the sheath liquid flow meet can be ensured. Slightly larger than the sheath flow, preventing the sample flow from being scattered by the sheath flow, keeping the flow stable, and ensuring the two-dimensional focusing effect of the sample flow.

In addition, the microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the present invention may further have the following additional technical features:

According to an embodiment of the invention, the two laterally focused flow channels are bilaterally symmetrical about a longitudinal center section of the sample flow channel.

According to an embodiment of the invention, the upper longitudinal focusing flow channel and the lower longitudinal focusing flow channel are vertically symmetrical about a transverse central cross section of the sample flow channel.

According to an embodiment of the invention, the upper longitudinal focusing flow channel and/or the lower longitudinal focusing flow channel comprise: a linear flow channel portion, the linear flow channel portion and the sample flow channel in an up and down direction An upper alignment arrangement; a left arc flow path portion, the left arc flow path portion is disposed on a left side of the linear flow path portion, and a front end of the left arc flow path portion and the linear flow The rear end of the road portion is tangent and connected; the right side curved flow path portion is disposed on the right side of the straight flow path portion, and the right curved portion of the flow path portion a front end tangentially and in communication with a rear end of the linear flow path portion, the outer contour lines of the upper longitudinal flow channel and the lower longitudinal flow flow channel being opposite to the two lateral focus flow channels The outer contour lines are arranged in alignment in the up and down direction.

According to an embodiment of the present invention, a front end of the left arc runner portion communicates with a front end of the right arc runner portion, and the left arc runner portion and the right arc portion The angle between the inner contours of the intersection of the flow passages is α, 50° ≤ α ≤ 80°.

According to an embodiment of the present invention, the front end face of the straight flow path portion forms a plane or a non-planar shape in which the middle portion projects forward.

According to an embodiment of the present invention, the two lateral focusing flow channels respectively form arcs arranged opposite each other, and the width of each of the lateral focusing flow channels is larger than the left arc flow path portion and the The width of the right arc flow path portion.

According to an embodiment of the invention, the opposite outer contour lines and the opposite inner contour lines of the two laterally focused flow channels are respectively disposed tangent to the outer contour line of the sample flow channel.

According to an embodiment of the invention, the longitudinal thickness of the sample flow channel is equal to the longitudinal thickness of the two laterally focused flow channels, the upper longitudinal focusing flow channel and the lower longitudinal focusing flow channel The longitudinal thickness is equal.

According to an embodiment of the invention, the longitudinal thickness of the sample flow channel is equal to the longitudinal thickness of the upper longitudinal focusing flow channel / the lower longitudinal focusing flow channel.

According to an embodiment of the invention, the longitudinal thickness of the sample flow channel is not equal to the longitudinal thickness of the upper longitudinal focusing flow channel / the lower longitudinal focusing flow channel.

According to an embodiment of the present invention, further comprising two focus stream inlets, the two focus stream inlets and the two of the lateral focusing stream channels, the upper layer longitudinal focusing stream channel and the lower layer longitudinal focusing stream The flow channels are in communication and the two focused flow inlets are in communication with a source of liquid flow through the conduit.

A microfluidic chip according to an embodiment of the second aspect of the present invention includes the microfluidic structure that realizes two-dimensional hydrodynamic focusing using a single sheath liquid according to the above embodiment.

According to an embodiment of the present invention, a first sheet body having the sample flow channel and two of the lateral focusing flow channels formed on the first sheet; a second sheet, the second a sheet body is stacked on the first sheet body, and the second sheet body is formed with the upper layer longitudinal focusing flow channel; a third sheet body, the third sheet body is stacked on the first sheet a lower surface of the body, and the lower layer longitudinal focusing flow channel is formed on the third body; an upper cover, the upper cover is stacked above the second body; a lower cover, the lower a cover is stacked under the third piece, and at least one of the upper cover and the lower cover is provided with a focus flow injection port, a sample flow injection port communicating with the sample flow inlet, and the liquid The output port through which the outflow port is connected.

The additional aspects and advantages of the invention will be set forth in part in the description which follows.

DRAWINGS

1 is a schematic structural view of a microchannel structure according to an embodiment of the present invention;

Figure 2 is an exploded view of the microchannel structure shown in Figure 1;

3 is a schematic structural view of a microchannel structure and a cross-sectional view at different positions according to an embodiment of the present invention;

4 is a schematic structural view of a microchannel structure according to still another embodiment of the present invention;

Figure 5 is a plan view of the microchannel structure shown in Figure 1;

Figure 6 is a schematic structural view and a partial enlarged view of the microchannel structure shown in Figure 1;

Figure 7 is a schematic structural view and a cross-sectional view of the microchannel structure shown in Figure 1;

Figure 8 is a perspective view of a microfluidic chip in accordance with an embodiment of the present invention;

Figure 9 is an exploded view of the structure shown in Figure 8.

Reference mark:

a: sample flow; b: sheath flow; c: flow source;

1: microfluidic chip;

100: microchannel structure;

111: sample flow channel; 111a: sample flow inlet; 111b: liquid flow outlet;

112: a lateral focusing flow path; 112a: a focusing flow inlet;

120: an upper longitudinal focusing flow channel;

121 (131): straight flow channel section;

122 (132): the left arc runner portion;

123 (133): the right side of the arc channel;

130: a lower longitudinal focusing flow channel;

210: a first sheet; 220: a second sheet; 230: a third sheet; 240: an upper cover; 241: a sample flow injection port;

242: output port; 243: focus flow injection port; 244: through hole; 245: observation window; 250: lower cover.

detailed description

Embodiments of the invention are described in detail below, examples of which are illustrated in the accompanying drawings. The embodiments described below with reference to the drawings are intended to be illustrative of the invention and are not to be construed as limiting.

A microchannel structure 100 for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the first aspect of the present invention will be specifically described below with reference to FIGS. 1 through 7.

As shown in FIG. 1, a microchannel structure 100 for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the present invention includes a sample flow channel 111, two lateral focusing flow channels 112, and an upper longitudinal focusing flow. The track 120 and the lower layer longitudinally focus the flow channel 130. Specifically, the sample flow path 111 extends in a straight line in the front-rear direction, both ends of the sample flow path 111 form a sample inflow port 111a and a liquid outflow port 111b, and the upper layer longitudinal in-focus flow path 120 is superposed on the sample flow path 111. Above and in communication with the sample flow channel 111, the lower longitudinal focusing flow channel 130 is superposed below the sample flow channel 111 and is in communication with the sample flow channel 111, and the two laterally focused flow channels 112 are respectively disposed in the sample flow. The left and right sides of the flow path 111 are respectively connected to the sample flow channel 111, the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130, and each lateral focusing flow channel 112 is in the flow direction, The width gradually decreases from the back to the front, and the maximum width of each of the lateral focusing flow passages 112 is larger than the width of the sample flow path 111.

Optionally, the sample flow channel 111, the two laterally focused flow channels 112, the upper longitudinally focused flow channel 120, and the lower longitudinally focused flow channel 130 of the microchannel structure 100 may be shells of the microchannel structure 100. The body defines, preferably, the sample flow channel 111 is formed in a straight line extending in the front-rear direction, and the sample flow channel 111 has the same cross-sectional shape and equal cross-sectional area at different positions, wherein the rear end of the sample flow channel 111 Forming a sample inflow port 111a, the sample stream channel 111 The front end forms a liquid flow outlet 111b, and the sample flow flow path 111 can be used to flow the sample flow a and the focusing liquid (for example, the sheath liquid flow b).

Two lateral focusing flow channels 112 are respectively disposed on the left and right sides of the sample flow channel 111 and two lateral focusing flow channels 112 are respectively connected to the sample flow channel 111, and the sample stream a enters the sample flow from the sample inlet 111a. In the channel 111, the sheath liquid stream b enters the lateral focusing flow path 112, the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 on the left and right sides from the focusing flow inlet 112a, and the sample flow a is first located in the sample flow. The sheath liquid flow b in the lateral focusing flow channel 112 on the left and right sides of the track 111 contacts, and as the lateral focusing flow channel 112 gradually narrows, the sheath liquid flow b symmetrically squeezes the sample flow a and keeps the sample flow a at The lateral centering of the sample stream a (focusing in the left and right direction) is achieved by right and left center position and reducing its lateral dimension.

The upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 are respectively disposed on upper and lower sides of the sample flow channel 111, and the upper longitudinal focusing flow channel 120 is located above the two lateral focusing flow channels 112 and The lateral focusing flow channels 112 are in communication, and the lower longitudinal focusing flow channels 130 are located below the two lateral focusing flow channels 112 and are in communication with the two lateral focusing flow channels 112, above and below the sample flow channel 111. The longitudinal fluid flow path 120 and the sheath liquid flow b in the lower longitudinal flow flow channel 130 symmetrically press the liquid flow (sample flow a and sheath liquid flow b) located in the middle flow path to ensure that they are in the upper and lower center positions. Thereby, the longitudinal focusing (focusing in the up and down direction) of the sample stream a is achieved. Subsequently, the sample stream a enters the front section of the sample flow channel 111 under the sheath of the sheath fluid stream b, and is stably located at the central cross-sectional position of the sample flow channel 111, facilitating various types of photodetection of the sample stream a.

That is, the microchannel structure 100 is a three-layer flow channel structure, and the three-layer flow channels are connected to each other without an interface, wherein the sample flow channel 111 and the lateral focusing flow disposed on the left and right sides of the sample flow channel 111 The flow channel 112 is located in the middle layer, and as the sheath liquid flow b in the two laterally focused flow channels 112 flows from the back to the front, the sheath liquid flow b in the two laterally focused flow channels 112 can achieve the sample flow a. The lateral focusing, the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 are respectively located in the upper layer and the lower layer, and the end (front end) of the two longitudinal focusing flow channels are merged into the sample flow channel 111 in the middle layer, along with The thickness of the two longitudinal focusing flow channels (the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130) is reduced, and the sheath liquid flow b in the two longitudinal focusing flow channels is incorporated into the sample flow channel 111, Longitudinal focusing of the sample stream a can be achieved.

Thus, the microchannel structure 100 for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the present invention, the two lateral focusing flow channels 112 are disposed on the left and right sides of the sample focusing flow channel, so that the sample The stream a may first achieve lateral focusing, that is, compressing the size of the sample stream a in the lateral direction (the left and right direction as shown in FIG. 1), and setting the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 respectively. Positioning above and below the lateral focusing flow channel 112 allows the sample stream a to achieve longitudinal focusing, i.e., when the sheath flow b in the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 symmetrically enters the middle The sample flow channel 111 of the layer can compress the longitudinal dimension of the sample stream a to achieve a two-dimensional focus of the sample stream a as a whole, since the flow of the sheath fluid stream b is much larger than the flow of the sample stream a, the laterally focused flow channel The width of 112 is set to be larger than the width of the sample flow channel 111, and it is ensured that when the sample stream a and the sheath liquid stream b meet, The velocity/dynamic pressure of the sample stream a is slightly larger than the sheath fluid flow b, preventing the sample flow a from being scattered by the sheath liquid flow b, keeping the liquid flow stable, and ensuring the two-dimensional focusing effect of the sample flow a.

Preferably, according to one embodiment of the invention, the two laterally focused flow channels 112 are bilaterally symmetric about the longitudinal center section of the sample flow channel 111. The upper longitudinal focusing flow passage 120 and the lower longitudinal focusing flow passage 130 are vertically symmetrical with respect to the transverse center cross section of the sample flow passage 111.

That is to say, the microchannel structure 100 of the embodiment of the present invention is mainly composed of three layers of microchannels, which are left and right and up and down symmetric as a whole, and the three layers of microchannels are vertically connected and there is no interface, and the first is located above. The structure of the layer microchannel (upper layer longitudinal focusing flow channel 120) is the same as that of the third layer microchannel (lower layer longitudinal focusing channel 130) located below, and the two laterally focusing flow channels 112 in the middle The structure is the same. In operation, the sample stream a enters the sample flow channel 111 in the upper and lower direction from the sample stream inlet 111a, and the sheath liquid stream b enters the laterally focused flow channel 112 on the left and right sides from the focus stream inlet 112a, and the upper layer longitudinal direction. In the focusing flow channel 120 and the lower longitudinal focusing flow channel 130, the sample stream a sequentially achieves lateral focusing and longitudinal focusing under the action of the sheath fluid flow b, that is, achieving two-dimensional focusing. Thus, by arranging the two lateral focusing flow channels 112, the upper longitudinal focusing flow channel 120, and the lower longitudinal focusing flow channel 130 symmetrically in the left and right, up and down orientations of the sample flow channel 111, the longitudinal focusing flow path can be ensured. The sheath fluid flow b pressure changes synchronously with the liquid flow pressure in the lateral focusing flow channel 112 to maintain the liquid flow stability, thereby ensuring the two-dimensional focusing effect of the sample flow a.

Wherein, as shown in FIG. 2, according to an embodiment of the present invention, the upper longitudinal focusing flow channel 120 and/or the lower longitudinal focusing flow channel 130 includes a linear flow path portion 121 (131) and a left curved flow path portion. 122 (132) and the right arc runner portion 123 (133). Specifically, the linear flow path portion 121 (131) and the sample flow channel 111 are arranged in the vertical direction, and the left arc flow path portion 122 (132) is provided on the left side of the linear flow path portion 121 (131). The front end of the left arc flow path portion 122 (132) is tangentially connected to the rear end of the linear flow path portion 121, and the right curved flow path portion 123 (133) is provided in the linear flow path portion 121 (131). On the right side, the front end of the right arc flow path portion 123 (133) is tangentially and in communication with the rear end of the linear flow path portion 121 (131), and the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 are The outer contour line opposite to the two lateral focusing flow passages 112 is aligned in the up and down direction.

In other words, the upper longitudinal focusing flow channel 120 is mainly composed of a linear flow path portion 121 located above the sample flow channel 111 and a left arc flow path portion 122 and a right arc flow above the two laterally focused flow channels 112. The track portion 123 is composed of a lower portion longitudinal focusing flow path 130 mainly composed of a straight flow path portion 131 located below the sample flow path 111 and a left arc flow path portion 132 and a right side located below the two laterally focused flow paths 112. The arc flow path portion 133 is composed of. Wherein, the upper left arc channel portion 122 and the right arc channel portion 123 are respectively disposed tangentially and in communication with the upper straight channel portion 121 and are respectively positioned with the two lateral focusing channels 112 One-to-one correspondence, the left arc flow path portion 132 and the right arc flow path portion 133 located below are disposed tangentially and in communication with the linear flow path portion 131 located below and respectively with the two lateral focus flow paths 112 The position of the one-to-one correspondence.

In operation, the sample stream a enters the sample flow channel 111 from the sample stream inlet 111a, and the sheath fluid stream b is from the focused stream inlet. 112a enters the lateral focusing flow channel 112, the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 on the left and right sides. First, the sample stream a and the lateral focusing flow located on the left and right sides of the sample flow channel 111 The sheath fluid flow b in the channel 112 is contacted, and as the lateral focusing flow channel 112 is gradually narrowed, the sheath fluid flow b symmetrically presses the sample flow a symmetrically, maintains it at the left and right center position, and reduces its lateral dimension. The lateral focus of the sample stream a. Subsequently, the sheath liquid flow b in the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 above and below the sample flow channel 111 squeezes the liquid flow in the central flow channel symmetrically up and down (sample flow a and The sheath fluid stream b) is guaranteed to be in the up and down center position, and as the longitudinal dimension of the linear flow path portion 121 (131) is reduced, longitudinal focusing of the sample stream a is achieved. The sample stream a is focused in both the lateral and longitudinal directions, completing the two-dimensional focus.

Subsequently, the outer periphery of the sample stream a enters the front portion of the sample flow channel 111 under the sheath of the sheath fluid stream b, and is stably located at the central cross-sectional position of the sample flow channel 111, facilitating various types of photodetection of the sample stream a. In operation, the lateral focusing flow path 112 entering the left and right sides and the sheath liquid flow b of the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 of the upper and lower sides are symmetrically distributed, so that the sheath liquid flow b can be powered by one The source drive, that is, the two-dimensional hydrodynamic focusing is realized by using a single sheath liquid. By selecting different structural parameters and adjusting the flow rate, the microchannel structure 100 of the embodiment of the present invention can be at a central flow rate of several meters per second. The sample stream a is focused to a few micrometers to more than twenty micrometers (the feature size of the cross section of the sample stream a), achieving effective focusing at high flow rates and meeting high speed detection requirements.

Thereby, the lateral focusing flow channel 112, the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 are electrically connected to each other, and the opposite outer contours of the two lateral focusing flow channels 112 are aligned with the two longitudinal directions. The opposite outer contours of the flow channels (the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130) are disposed the same to ensure the sheath fluid flow b pressure of the longitudinal focusing flow channel and the lateral focusing flow channel 112. The flow pressure changes synchronously and the liquid flow is maintained.

Alternatively, according to an embodiment of the present invention, the front end of the left arc runner portion 122 (132) communicates with the front end of the right arc runner portion 123 (133), and the left arc runner portion 122 The angle between the inner contour line of the intersection A of (132) and the right arc flow path portion 123 (133) is α, 50° ≤ α ≤ 80°.

Referring to Fig. 5, the left arc flow path portion 122 and the right arc flow path portion 123 of the upper longitudinal flow channel 120 gradually merge from rear to front and have a straight flow of the front end and the upper longitudinal flow path 120. The rear end of the road portion 121 is communicated, and the left side arc flow path portion 132 and the right side curved flow path portion 133 of the lower longitudinal flow channel 130 are gradually merged from the back to the front and the front end and the lower longitudinal flow path are merged. The linear flow path portion 131 of 130 is in communication.

Wherein, the angle between the inner contour line of the intersection of the left arc runner portion 122 (132) and the right arc runner portion 123 (133) is controlled between 50° and 80°, for example, 50°. 60° or 80°, so that the intersection A of the left arc runner portion 122 (132) and the right arc runner portion 123 (133) has a certain length L, which can be known from the experiment: The flow path profile of the intersection A of the side arc flow path portion 122 (132) and the right arc flow path portion 123 (133) needs to meet a special requirement: the intersection A contour needs to maintain an appropriate length L in the front and rear direction; The length L of the intersection A contour is too long to increase the sheath flow b in the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130. The lateral extrusion of the flow a reduces the longitudinal extrusion, thereby increasing the height dimension of the cross section of the sample stream a after focusing; if the length L of the junction A contour is too short, the left arc runner portion 122 (132) and the right The sheath fluid flow in the side-arc flow passage portion 123 (133) cannot meet in time due to inertia, and a local low pressure is generated at the junction A while the second-layer micro-flow passage (sample flow passage 111 and two lateral directions) The flow in the focusing flow channel 112) expands into the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130, which also increases the height dimension of the section of the sample stream a after focusing.

Thus, by controlling the angle of the A contour at the intersection of the left arc runner portion 122 (132) and the right arc runner portion 123 (133) to be between 50° and 80°, the sample flow can be ensured. The left arc flow path portion 122 and the right arc flow path portion 123 above the flow path 111, the intersection of the left arc flow path portion 132 and the right side curved flow path portion 133 located below the sample flow path 111 A has an appropriate length L such that the sheath flow b in the left arc flow path portion 122 (132) and the right arc flow path portion 123 (133) merges with each other in the up and down direction, right and left. The sample stream a coated on both sides with the sheath flow b is extruded to effectively stabilize the two sheath streams b combined with the sample stream a, which helps to enhance the longitudinal focusing of the sample stream a to be carried out downstream. Thereby the longitudinal focusing effect of the sheath flow b on the sample stream a is ensured.

Alternatively, as shown in part B of Fig. 6, according to an embodiment of the present invention, the front end face of the straight flow path portion 121 forms a plane or a non-planar shape in which the middle portion projects forward. In operation, the left side arc flow path portion 122 of the upper longitudinal flow channel 120 above the two lateral focus flow channels 112 and the sheath liquid flow b in the right arc flow path portion 123 at the end of the intersection And entering the linear flow path portion 121 above the sample flow channel 111, the left arc flow channel portion 132 and the right arc flow channel of the lower longitudinal flow channel 130 below the two laterally focused flow channels 112. The sheath liquid flow b in the portion 133 enters the straight flow path portion 131 located below the sample flow path 111 at the intersection of the two.

In some specific example examples of the present invention, the front end faces of the straight flow path portions 121 (131) on the upper and lower sides are formed into a plane, which can effect the longitudinal focusing of the sample stream a; in other specific examples of the present invention The front end faces of the two straight flow path portions 121 (131) may form a non-planar shape in which the central portion protrudes forward, for example, if the front end surface of the straight flow path portion 121 (131) forms a centrally convex forward and symmetrical folded surface That is, two intersecting planes are formed, such that the sheath fluid flow b forms four symmetrical vortices having a longitudinal compression effect in a section of the flow path which is a distance, which further enhances the longitudinal focusing effect on the sample stream a.

Preferably, as shown in FIG. 7, the front end surface of the linear flow path portion 121 of the upper longitudinal flow channel 120 and the front end surface of the linear flow path portion 131 of the lower longitudinal flow path 130 are formed to protrude in the middle. The curved surface, such that the sheath flow b forms four vortices having a longitudinal compression effect symmetrical in the up and down direction and the left and right direction in a flow path section of a distance, in the process, with the upper longitudinal flow stream The thickness of the channel 120 and the lower longitudinal focusing flow channel 130 is reduced, and the sheath fluid b compresses the longitudinal dimension of the sample stream a to achieve longitudinal focusing of the sample stream a. Further, the four eddy currents of the sheath stream b The longitudinal focusing of the sample stream a is further enhanced to ensure the effect of longitudinal focusing of the sample stream a. Specifically, different end profiles can be selected according to different flow rates and desired sizes after the sample stream a is focused.

Thus, by setting the front end surface of the straight flow path portion 121 (131) to a non-planar shape in which the central portion is convex forward, it is possible to The sheath fluid stream b forms four symmetrical vortices having a longitudinal compression effect in the cross section of the sample flow channel 111, which vortexes can further enhance the longitudinal focusing effect on the sample stream a.

Optionally, in accordance with an embodiment of the present invention, the two lateral focusing flow channels 112 are respectively formed in opposite arcuate shapes, and each of the lateral focusing flow channels 112 has a width greater than the left curved channel portion 122 ( 132) and the width of the right arc runner portion 123 (133).

In other words, the sample flow channel 111 forms a DC channel extending in the front-rear direction, two laterally focused flow channels 112 are disposed on the left and right sides of the sample flow channel 111, and the two laterally focused flow channels 112 form two intersecting arcs. The micro flow channel, the left arc flow channel portion 122 and the right arc channel portion 123 of the upper longitudinal focusing flow channel 120 above the sample flow channel 111, and the lower layer longitudinal focus under the sample flow channel 111 The left arc flow path portion 132 and the right side curved flow path portion 133 of the flow path 130 respectively form arcuate micro flow paths corresponding to the outer contours of the two lateral focus flow paths 112. The width of the lateral focusing flow path 112 is set to be larger than the width of the left arc flow path portion 132 and the right side curved flow path portion 133 such that the sheath liquid flow b in the two laterally focused flow channels 112 is first in the liquid The flow direction gradually merges. During operation, the sheath liquid flow b in the lateral focusing flow path 112 on the left and right sides of the sample flow path 111 first comes into contact with the sample flow a, and gradually narrows as the lateral focusing flow path 112 gradually narrows. The sheath fluid stream b squashes the sample stream a symmetrically, maintains it at the left and right center positions, and reduces its lateral dimension, achieving lateral focusing of the sample stream a. The sheath flow b in the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 is then squeezed up and down symmetrically to effect longitudinal focusing of the sample stream a.

Thereby, two lateral focusing flow channels 112 are symmetrically disposed on the left and right sides of the sample flow channel 111 to focus the sample stream a at the center position, and the sheath liquid is introduced into the bilaterally symmetric lateral focusing flow channel 112. The flow b can achieve lateral focusing of the sample stream a; since the flow rate of the sheath liquid flow b is much larger than the flow rate of the sample flow a, setting the width of the lateral focusing flow path 112 to be larger than the width of the sample flow path 111 ensures When the sample stream a and the sheath liquid stream b meet, the velocity/dynamic pressure of the sample stream a is slightly larger than the sheath liquid flow b, and the sample stream a is prevented from being scattered by the sheath liquid stream b. Setting the width of the lateral focusing flow channel 112 to be larger than the width of the left arc channel portion 122 (132) or the right arc channel portion 123 (133) is advantageous for ensuring that the sample stream a is first laterally focused. In the case where the lateral focus is stable, longitudinal focusing is performed on the sample stream a, and the two-dimensional focusing effect of the sample stream a is improved.

Preferably, in accordance with an embodiment of the present invention, the opposite outer contour lines and the opposite inner contour lines of the two lateral focusing flow channels 112 are respectively disposed tangent to the outer contour lines of the sample flow channel 111. Thereby, the two lateral focusing flow channels 112 are tangential to the sample flow channel 111 and slowly merged into the intermediate sample flow channel 111 in the front-rear direction, which can constrain the sheath fluid b to maintain the layer during focusing and steering. The flow state and flow direction change smoothly, and the flow line has no abrupt change, thereby reducing flow resistance and improving system stability. The long intersection between the lateral focusing flow channel 112 and the sample flow channel 111 allows the sample stream a to reach a stable lateral focus state before the confluence of the sheath fluid stream b in the longitudinal focusing flow channel to ensure the flow. Stability.

Wherein, according to an embodiment of the present invention, the longitudinal thickness of the sample flow channel 111 and the two laterally focused flow channels The longitudinal thicknesses of 112 are equal, and the longitudinal thicknesses of the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 are equal. Thereby, the stability of the lateral focus is ensured, and the longitudinal thicknesses of the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130 are equal, thereby ensuring the stability of the longitudinal focusing.

In some embodiments of the invention, the longitudinal thickness of the sample flow channel 111 is equal to the longitudinal thickness of the upper longitudinal focusing flow channel 120 / the lower longitudinal focusing flow channel 130. In other words, the upper longitudinal focusing flow channel 120 located above the two lateral focusing flow channels 112 and the lower longitudinal focusing flow channel 130 located below the two lateral focusing flow channels 112 are equal in thickness in the up and down direction, and The thickness of the upper longitudinal focusing flow channel 120 and the thickness of the lower longitudinal focusing flow channel 130 are equal to the thickness of the sample flow channel 111 and the two lateral focusing flow channels 112, respectively, on the entirety of the microchannel structure 100, The thickness of the layer microchannels is equal, which satisfies the requirement of focusing the sample stream a at the vertical center.

In other embodiments of the invention, the longitudinal thickness of the sample flow channel 111 is not equal to the longitudinal thickness of the upper longitudinal focusing flow channel 120 / the lower longitudinal focusing flow channel 130. In other words, the upper longitudinal focusing flow channel 120 located above the two lateral focusing flow channels 112 and the lower longitudinal focusing flow channel 130 located below the two lateral focusing flow channels 112 are equal in thickness in the up and down direction, and The thickness of the upper longitudinal focusing flow channel 120 and the thickness of the lower longitudinal focusing flow channel 130 are not equal to the thickness of the sample flow channel 111 and the two lateral focusing flow channels 112, respectively, on the entirety of the microchannel structure 100, The thickness of the microchannels located above and below is not equal to the thickness of the microchannels located in the middle. By adjusting the thickness of the longitudinal focusing flow channel, the flow rate of the sheath fluid b in the longitudinal focusing flow channel can be increased or decreased, thereby Enhances or reduces the longitudinal focusing effect on the sample stream a.

Wherein, according to an embodiment of the present invention, there are further included two focusing stream inlets 112a, two focusing stream inlets 112a and two lateral focusing stream channels 112, an upper layer longitudinal focusing stream channel 120 and a lower layer longitudinal focusing stream channel, respectively. 130 is connected, and the two focus flow inlets 112a are in communication with a liquid flow source c through a pipeline.

Specifically, as shown in FIG. 1, the rear end of the lateral focusing flow path 112 on the left side of the sample stream a, the rear end of the left side arc flow path portion 122 of the upper layer longitudinal direction 120, and the lower layer longitudinal focusing flow path 130 are shown. The rear end of the left arc flow path portion 132 forms a focusing flow inlet 112a, that is, the focusing flow inlet 112a simultaneously with the lateral focusing flow path 112 on the left side, the upper longitudinal focusing flow path 120, and the lower longitudinal focusing flow. The rear end of the flow path 130 is turned on, the rear end of the lateral focusing flow path 112 on the right side of the sample stream a, the rear end of the right side arc flow path portion 123 of the upper layer longitudinal direction 120, and the lower layer longitudinal focusing flow path 130. The rear end of the right arc flow path portion 133 forms another focusing flow inlet 112a, that is, the focusing flow inlet 112a simultaneously with the lateral focusing flow path 112 on the right side, the upper longitudinal focusing flow path 120, and the lower longitudinal focusing flow The rear end of the flow path 130 is turned on.

Wherein, the sheath fluid flow b can be driven by a power source through the two focus flow inlets 112a into the left and right symmetrical lateral focusing flow channels 112 and the upper and lower symmetrical upper longitudinal focusing flow channels 120 and the lower longitudinal focusing flow channels 130, That is, the two-dimensional hydrodynamic focusing is realized by a single sheath liquid, and the symmetric distribution of the sheath fluid flow b is ensured. The microchannel structure 100 is capable of focusing the sample stream a to a characteristic size of its cross section of several micrometers to twenty micrometers at a central flow rate of several meters per second, that is, Effective focusing at high flow rates.

A microchannel structure 100 for achieving two-dimensional hydrodynamic focusing using a single sheath fluid in accordance with an embodiment of the present invention is specifically described below in conjunction with various embodiments.

The microchannel structure 100 is symmetrical on the whole, and is vertically symmetrical, and is composed of three layers of microchannels. The three layers of microchannels are vertically connected and there is no interface. The second layer of microchannels is first. Between the layer microchannel and the third layer microchannel, the first layer and the third layer microchannel have the same structure, as shown in FIG. 3, the first layer microchannel is the upper layer longitudinal focusing channel 120, wherein The upper longitudinal focusing flow channel 120 includes a linear flow path portion 121 and two intersecting left arc flow channel portions 122 and a right arc flow channel portion 123, and the third layer micro flow channel is a lower layer longitudinal focusing flow channel 130. The lower layer longitudinal focusing flow path 130 includes a linear flow path portion 131 and two intersecting left arc flow path portions 132 and a right arc flow path portion 133, and the second layer micro flow path is mainly located at an intermediate position The sample flow channel 111 and the two curved lateral focusing flow channels 112 that flow into the sample flow channel 111, and the width of the lateral focusing flow channel 112 is greater than the width of the sample flow channel 111; All of the curved microchannels in the flow channel have the same outer contour.

In operation, the sample stream a enters from the sample stream inlet 111a of the sample stream channel 111, and the sheath liquid stream b enters the arcuate microchannels on the left and right sides from the focus stream inlet 112a (including the left and right sides of the sample stream channel 111). The lateral focusing flow channel 112, the upper longitudinal focusing flow channel 120 and the lower longitudinal focusing flow channel 130), the sample stream a sequentially achieves lateral focusing and longitudinal focusing under the action of the sheath fluid b, ie two-dimensional focusing. First, the sample stream a is in contact with the sheath liquid stream b in the two arcuate microchannels (the lateral focusing flow channel 112) of the second layer, and the sheath liquid stream b is gradually narrowed as the lateral focusing flow channel 112 is gradually narrowed. The sample stream a is symmetrically squeezed, held in the left and right center position, and its lateral dimension is reduced, achieving lateral focusing of the sample stream a, as shown in the flow channel section of FIG.

Subsequently, at the end of the lateral focusing flow path 112 (the front end as shown in FIG. 3), the first layer micro flow path (upper layer longitudinal focusing flow path 120) and the third layer micro flow path (lower layer longitudinal focusing flow path) The sheath liquid stream b in 130) enters into the second layer microchannel, and squeezes the liquid flow in the second layer microchannel symmetrically up and down symmetrically, maintains it in the upper and lower center position, and reduces its longitudinal dimension, thereby achieving Longitudinal focusing of sample stream a. The sample stream a is focused in both the lateral and longitudinal directions, completing the two-dimensional focus. Thereafter, the sample stream a enters the anterior segment of the sample flow channel 111 under the sheath of the sheath fluid stream b, and is stably located at the center of the cross section of the sample flow channel 111, as shown in the flow channel section in Fig. 3, thereby facilitating the flow of the sample. a Conduct various types of photoelectric detection. Preferably, as shown in FIG. 4, in operation, the sheath liquid flow b entering the arcuate microchannels on the left and right sides is symmetrically distributed, and thus the sheath fluid flow b can be supplied from a liquid flow source c, that is, using a single sheath liquid. Two-dimensional hydrodynamic focusing.

Embodiment 1

The first layer of microchannels and the third layer of microchannels are in communication with the microchannels of the second layer and have the same outer contour to ensure the sheath fluid flow b pressure and the liquid in the second layer microchannel The flow pressure changes synchronously and maintains the stability of the liquid flow in the system; the first layer of micro flow channels (upper layer longitudinal focusing flow channel 120) or the third layer of micro flow channels (lower layer longitudinal focusing flow channel 130) The contour of the flow path at the intersection of the two curved microchannels (the left arc runner portion 122 (132) and the right arc runner portion 123 (133)) needs to maintain an appropriate length L in the front and rear directions. If the length is too long, the lateral flow of the sheath flow b in the first layer microchannel and the third microchannel will increase the lateral extrusion of the sample stream a, weaken the longitudinal extrusion, and increase the height dimension of the section after the sample stream a is focused. If the length is too short, the sheath liquid flow b in the curved micro flow channel cannot meet in time due to inertia, local low pressure is generated at the junction A, and the liquid flow in the second micro flow channel is directed to the first layer micro flow channel and the third layer. The height of the post-focus section of the sample stream a is expanded and increased in the microchannel. Therefore, the left arc runner portion 122 (132) and the right arc runner portion 123 of the microchannel structure 100 of the embodiment of the present invention. The flow path profile at the intersection of (133) adopts an α=50°-80° structure, thereby solving the above problem.

Specifically, in this embodiment, the height of the second layer microchannel is equal to the height of the first layer microchannel and the third layer microchannel, and the height of the three layer microchannels is selected to be 150 μm, which is located at the second The width of the sample flow channel 111 of the layer is selected to be 300 μm, and the inner contour of the flow path of the intersection of the two curved microchannels in the first layer microchannel or the third layer microchannel is selected to be 70°, which is located in the sample. The front end faces of the two straight flow path portions 121 (131) above and below the flow channel 111 are curved faces, and the micro flow channel structure 100 enables high-speed focusing, and the flow rate of the sample flow a after focusing is up to several meters per second.

First, the sample flow a flow rate is 0.5 μL/s, and the sheath liquid flow b flow rate is 120 μL/s. The sample flow a is subjected to a two-dimensional focusing experiment. Then, the sample flow a after focusing is approximately 12 μm × 12 μm (width × The square of the high) sample flow a has a flow rate of 5.1 m/s.

The sample flow a flow rate is 1 μL/s, the sheath liquid flow b flow rate is 100 μL/s, and then the cross-sectional shape of the sample flow a after focusing is approximately 13 μm×24 μm (width×height) rectangle. At this time, the sample flow a is located in the flow. At the center of the track, the flow rate of sample stream a reached 4.3 m/s.

The sample flow a flow rate is 1 μL/s, the sheath liquid flow b flow rate is 120 μL/s, and then the cross-sectional shape of the sample flow a after focusing is approximately 17 μm × 14 μm (width × height), and the flow rate of the sample flow a reaches 5.1 m. /s.

As an experiment, the microchannel structure 100 is capable of adjusting the cross-sectional size of the sample stream a after focusing by adjusting the flow rate of the sample stream a and the flow rate of the sheath stream b.

Embodiment 2

In the present embodiment, the heights of the first layer microchannel and the third layer microchannel are equal to meet the requirement of focusing the sample stream a at the vertical center. The height of the second layer microchannel may be different from the height of the first layer and the third layer microchannel, keeping the height of the second layer microchannel constant, by simultaneously increasing or decreasing the first layer microchannel and The height of the three-layer microchannel can increase or decrease the flow of the sheath fluid b in the two microchannels, thereby enhancing or reducing the longitudinal focusing effect on the sample stream a (correspondingly weakened to enhance the lateral direction of the sample stream a) Focusing effect).

Specifically, in this embodiment, the height of the second layer microchannel is 150 μm, and the first layer and the third layer microchannel may be different heights, and other dimensions are the same as those in the first embodiment. Select a sample flow a flow rate of 1 μL / s, sheath flow b flow rate of 140 μL / s, After focusing, the flow rate of the sample stream a reaches 6.1 m/s, and the sample stream a is located at the center of the flow channel. E.g:

The heights of the first layer microchannel and the third layer microchannel are selected to be 100 μm. At this time, the cross-sectional shape of the sample stream a after focusing is approximately 6 μm × 30 μm (width × height).

The height of the first layer microchannel and the third layer microchannel is 150 μm. At this time, the cross-sectional shape of the sample stream a after focusing is approximately 14 μm × 14 μm (width × height).

The heights of the first layer microchannel and the third layer microchannel are selected to be 200 μm. At this time, the cross-sectional shape of the sample stream a after focusing is approximately 22 μm × 9 μm (width × height).

It can be obtained that by simultaneously adjusting the heights of the first layer microchannel and the third layer microchannel, the cross-sectional size of the sample stream a after two-dimensional focusing can be changed, and the appropriate first layer microchannel and the first layer can be selected. The thickness of the three-layer microchannels achieves the desired two-dimensional focusing effect of the sample stream a.

Embodiment 3

As shown in FIG. 7, in the present embodiment, the sample flow a flow rate is 1 μL/s, the sheath liquid flow b flow rate is 120 μL/s, the flow rate of the sample flow a after focusing is 5.1 m/s, and the sample flow a is located in the flow path. At the center, the micro flow path structure 100 in which the front end surface of the straight flow path portion 121 (131) is a flat surface, a chamfer surface or a curved surface is selected, and the other dimensions are the same as those of the micro flow path structure 100 of the first embodiment.

When the front end surface of the linear flow path portion 121 (131) adopts a plane, the longitudinal focusing effect of the sheath liquid flow b in the first layer micro flow path and the third layer micro flow path on the sample flow a is limited, and the sample flow a is focused. The cross-sectional shape is approximately a rectangle of 6 μm × 50 μm (width × height).

When the front end surface of the straight flow path portion 121 (131) adopts a chamfered surface, the sheath liquid flow b forms four symmetrical vortices having a longitudinal compression effect in a section of the flow path which is further increased, and the eddy current further enhances the sample. The longitudinal focusing effect of the flow a is such that when the front end surface of the straight flow path portion 121 (131) is set to have an angle of 120°, the cross-sectional shape of the sample flow a after focusing is approximately 15 μm × 15 μm (width × height). .

When the front end surface of the linear flow path portion 121 (131) adopts a curved surface, the sheath liquid flow b also generates eddy current, further enhancing the longitudinal focusing of the sample flow a, such as the cross section of the sample flow a after the semicircular shape is selected. The shape is approximately a rectangle of 17 μm × 14 μm (width × height).

Experimentally, the microchannel structure 100 is capable of adjusting the cross-sectional size of the sample stream a after focusing by adjusting the contour shape of the front end surface of the straight flow path portion 121 (131), thereby obtaining different longitudinal directions of the sample stream a. Focus on the effect.

In summary, the microchannel structure 100 for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the present invention has a two-dimensional focusing function, and can focus by selecting different structural parameters and adjusting the flow rate of the liquid. The effect is controllable, and has the advantages of low flow resistance, wide flow range, etc., which can meet the requirements of high-speed detection. Furthermore, the micro-flow channel structure 100 can pass the inlets of the two sheath liquid streams b by using a single sheath liquid. Catheters, etc. are combined into one way and connected to one flow Source c to achieve two-dimensional hydrodynamic focusing.

The microfluidic chip 1 according to the second aspect of the present invention will be specifically described below with reference to FIGS. 1 through 9.

A microfluidic chip 1 according to an embodiment of the second aspect of the present invention includes a microchannel structure 100 for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to the above embodiment. Since the microchannel structure 100 for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to an embodiment of the present invention has the above-described technical effects, the microfluidic chip 1 according to an embodiment of the present invention also has the above-described technical effect, that is, the micro The fluid chip 1 has a simple structure and is easy to manufacture, and can be used for detecting biological particles such as cells, embryos, RNA, DNA, protein particles, microorganisms, viruses, etc. In the detection, the microfluidic chip 1 can stably carry a sample stream containing biological particles. Two-dimensional focusing is performed to focus on the center of the microchannel to improve the accuracy, sensitivity and stability of the detection.

Therein, an embodiment according to the present invention includes a first sheet 210, a second sheet 220, a third sheet 230, an upper cover 240, and a lower cover 250. Specifically, the first sheet body 210 is formed with a sample flow channel 111 and two lateral focusing flow channels 112. The second sheet 220 is stacked on the first sheet 210 and on the second sheet 220. An upper longitudinal focusing flow channel 120 is formed. The third body 230 is stacked under the first body 210, and the lower longitudinal focusing flow channel 130 is formed on the third body 230. The upper cover 240 is stacked on the first cover 240. Above the two-piece body 220, the lower cover 250 is stacked below the third body 230, and at least one of the upper cover 240 and the lower cover 250 is provided with a focused flow injection port 243, and a sample stream communicating with the sample inlet 111a. An inlet 241 and an output port 242 that communicates with the liquid outlet 111b.

Referring to FIGS. 8 and 9, the microfluidic chip 1 is mainly composed of a first sheet 210, a second sheet 220, a third sheet 230, an upper cover 240, and a lower cover 250. The upper cover 240, the second body 220, the first body 210, the third body 230, and the lower cover 250 are sequentially stacked from top to bottom, and the upper cover 240, the second body 220, and the first body 210 are disposed. The third body 230 and the lower cover 250 are provided with through holes 244 at four corners for facilitating the positioning and fixing of the microfluidic chip 1, and also by thermocompression bonding, gluing, bolt fastening, laser bonding, atomic bonding. And other means to achieve assembly. Optionally, the microfluidic chip 1 can be processed by using different materials such as glass, quartz, polymer, ceramic, and metal.

Specifically, as shown in FIG. 1 to FIG. 7 and FIG. 9, the first sheet body 210 is formed with a sample flow channel 111 and a lateral focusing flow channel 112 disposed on the left and right sides of the sample flow channel 111, and a second piece. The body 220 and the third body 230 are respectively disposed above and below the first sheet 210, and the second sheet 220 is formed with an upper longitudinal focusing flow channel 120, and the left side longitudinal focusing flow channel 120 is curved to the left side. The flow path portion 122 and the right curved flow path portion 123 are respectively located above the two lateral focusing flow channels 112 and are in conduction with the two lateral focusing flow channels 112, and the linear flow portion of the upper longitudinal focusing flow channel 120 121 is located above the sample flow channel 111 and is electrically connected to the sample flow channel 111. The outer side of the upper longitudinal focusing flow channel 120 is aligned with the two lateral focusing flow channels 112 and the sample flow channel 111 in the up and down direction. The third sheet body 230 is formed with a lower layer longitudinal focusing flow channel 130, and the left arc channel portion 132 and the right arc channel portion 133 of the lower layer longitudinal focusing channel 130 are respectively located in the two laterally focused streams. Below the track 112 and with the two lateral focusing flow channels 112, the lower layer is longitudinal The linear flow path portion 131 of the focusing flow channel 130 is located below the sample flow channel 111 and is electrically connected to the sample flow channel 111. The outer side of the lower longitudinal focusing flow channel 130 is in the up and down direction and the two laterally focused flow streams. The track 112 and the sample flow channel 111 are aligned, optionally, the two lateral focus flow channels 112, the upper longitudinal focus flow channel 120, and the left arc flow channel portion 122 of the lower longitudinal focus flow channel 130 (132). And the right arc flow channel portion 123 (133) respectively form an arc shape which is oppositely disposed and has the same outer contour, and the width of the lateral focus flow channel 112 is larger than the width of the sample flow channel 111 and the left arc flow channel portion, respectively. 122 (132) and the width of the right arc runner portion 123 (133).

Wherein, at least one of the upper cover 240 and the lower cover 250 of the microfluidic chip 1 is provided with a viewing window 245 for optical detection. One of the upper cover 240 and the lower cover 250 is provided with a sample flow injection port 241, an output port 242, and a focus flow injection port 243, wherein the sample flow injection port 241 is electrically connected to the sample inflow port 111a of the first sheet 210, and outputs The port 242 is electrically connected to the liquid outlet 111b of the first sheet 210, and the focusing stream injection port 243 is electrically connected to the focusing inlet 112a of the microchannel structure 100, and the focusing stream of the two sheath streams b can be injected into the port 243. Single sheath liquid focusing is achieved by merging the tubes outside the microfluidic chip 1 into one way and connecting to a liquid flow source c.

In use, the microchannel structure 100 of the first aspect of the present invention can be used as a functional module in the microfluidic chip 1, or can be separately designed as a microfluidic chip 1 dedicated to two-dimensional hydrodynamic focusing. The microfluidic chip 1 can be used as a functional device to form an open system platform with other devices, or to develop a portable instrument or device based on this, or to replace the hydrodynamic focusing device in a conventional instrument or device. .

The microfluidic chip 1 can be used to detect biological particles such as cells, embryos, RNA, DNA, protein particles, microorganisms, viruses, and the like. In the detection, the microfluidic chip 1 can stably focus the sample stream a containing the biological particles at the center of the microchannel to improve the accuracy, sensitivity and stability of the detection.

Other configurations and operations of the microfluidic chip 1 according to embodiments of the present invention are known to those of ordinary skill in the art and will not be described in detail herein.

In the description of the present invention, it is to be understood that the terms "center", "longitudinal", "transverse", "length", "width", "thickness", "upper", "lower", "front", " After, "Left", "Right", "Vertical", "Horizontal", "Top", "Bottom", "Inside", "Outside", "Clockwise", "Counterclockwise", "Axial", The orientation or positional relationship of the "radial", "circumferential" and the like is based on the orientation or positional relationship shown in the drawings, and is merely for convenience of description of the present invention and simplified description, and does not indicate or imply the indicated device or component. It must be constructed and operated in a particular orientation, and is not to be construed as limiting the invention.

Moreover, the terms "first" and "second" are used for descriptive purposes only and are not to be construed as indicating or implying a relative importance or implicitly indicating the number of technical features indicated. Thus, features defining "first" or "second" may include at least one of the features, either explicitly or implicitly. In the description of the present invention, the meaning of "a plurality" is at least two, such as two, three, etc., unless specifically defined otherwise.

In the present invention, the terms "installation", "connected", "connected", "fixed" and the like shall be understood broadly, and may be either a fixed connection or a detachable connection, unless explicitly stated and defined otherwise. Or integrated; can be mechanical The connections may also be electrically connected or communicated with each other; they may be directly connected or indirectly connected through an intermediate medium, and may be internal communication of two elements or an interaction relationship of two elements unless explicitly defined otherwise. For those skilled in the art, the specific meanings of the above terms in the present invention can be understood on a case-by-case basis.

In the present invention, the first feature "on" or "under" the second feature may be a direct contact of the first and second features, or the first and second features may be indirectly through an intermediate medium, unless otherwise explicitly stated and defined. contact. Moreover, the first feature "above", "above" and "above" the second feature may be that the first feature is directly above or above the second feature, or merely that the first feature level is higher than the second feature. The first feature "below", "below" and "below" the second feature may be that the first feature is directly below or obliquely below the second feature, or merely that the first feature level is less than the second feature.

In the description of the present specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" and the like means a specific feature described in connection with the embodiment or example. A structure, material or feature is included in at least one embodiment or example of the invention. In the present specification, the schematic representation of the above terms is not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in a suitable manner in any one or more embodiments or examples. In addition, various embodiments or examples described in the specification, as well as features of various embodiments or examples, may be combined and combined.

Although the embodiments of the present invention have been shown and described, it is understood that the above-described embodiments are illustrative and are not to be construed as limiting the scope of the invention. The embodiments are subject to variations, modifications, substitutions and variations.

Claims

A microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid, characterized in that it comprises:

a sample flow channel extending in a straight line in a front-rear direction, and a sample inlet and a liquid outlet are formed at both ends of the sample flow channel;

An upper longitudinal focusing flow channel, the upper longitudinal focusing flow channel being superposed above the sample flow channel and communicating with the sample flow channel;

a lower longitudinal focusing flow channel, the lower longitudinal focusing flow channel being superposed below the sample flow channel and in communication with the sample flow channel;

Two laterally focusing flow channels disposed on the left and right sides of the sample flow channel, respectively, and the sample flow channel and the upper longitudinal flow stream, respectively a channel and the lower layer longitudinal focusing flow channel are in communication, each of the lateral focusing flow channels gradually decreasing in a direction of a liquid flow from a back to a front, and a maximum width of each of the lateral focusing flow channels is greater than The width of the sample flow channel.
The microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 1, wherein the two lateral focusing flow channels are bilaterally symmetric with respect to a longitudinal center section of the sample flow channel .
A microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 1 or 2, wherein said upper longitudinal focusing flow channel and said lower longitudinal focusing flow channel are said The transverse center section of the sample flow channel is vertically symmetrical.
A microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to any one of claims 1 to 3, characterized in that the upper longitudinal focusing flow channel and/or the lower layer longitudinal focusing Flow channels include:

a linear flow path portion, the linear flow path portion being aligned with the sample flow channel in an up-and-down direction;

a left arc flow path portion, the left arc flow path portion is disposed on a left side of the linear flow path portion, and a front end of the left arc flow path portion and a rear portion of the linear flow path portion Tangent and connected;

a right arc flow path portion, the right arc flow path portion is disposed on a right side of the linear flow path portion, and a front end of the right arc flow path portion and a rear portion of the linear flow path portion Tangent and connected,

The outer contour lines of the upper longitudinal focusing flow channel and the lower longitudinal focusing flow channel are aligned with the outer contour lines opposite to the two lateral focusing flow channels in the up and down direction.
A microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 4, wherein a front end of said left arc flow path portion and said right curved flow path portion The front end is connected, and an angle between the inner contour line at the intersection of the left arc flow path portion and the right arc flow path portion is α, 50° ≤ α ≤ 80°.
The microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 4, wherein a front end surface of the linear flow path portion forms a plane or a non-planar surface in which the central portion protrudes forward.
The microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 4, wherein the two lateral focusing flow channels respectively form arcs arranged opposite each other, and each of the The width of the lateral focusing flow channel is greater than the width of the left arc channel portion and the right arc channel portion.
A microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath fluid according to claim 7, wherein opposite lateral contours and opposite inner contours of the two laterally focused flow channels They are respectively disposed tangent to the outer contour line of the sample flow channel.
A microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath fluid according to any one of claims 1-8, characterized in that the longitudinal thickness of the sample flow channel and the two lateral focusing The longitudinal thickness of the flow channels is equal, and the longitudinal thicknesses of the upper longitudinal focusing flow channels and the lower longitudinal focusing flow channels are equal.
A microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 9, wherein a longitudinal thickness of said sample flow channel and said upper longitudinal flow channel/lower layer The longitudinal thickness of the longitudinal focusing flow channels is equal.
A microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath liquid according to claim 9, wherein a longitudinal thickness of said sample flow channel and said upper longitudinal flow channel/lower layer The longitudinal thicknesses of the longitudinal focusing flow channels are not equal.
The microchannel structure for realizing two-dimensional hydrodynamic focusing using a single sheath liquid according to any one of claims 1 to 11, characterized in that it further comprises two focusing flow inlets, the two focusing flow inlets respectively And communicating with the two horizontally focused flow channels, the upper longitudinal focusing flow channel and the lower longitudinal focusing flow channel, the two focusing inlets being in communication with a liquid flow source through the pipeline.
A microfluidic chip comprising a microchannel structure for achieving two-dimensional hydrodynamic focusing using a single sheath fluid according to any one of claims 1-12.
The microfluidic chip of claim 13 comprising:

a first sheet on which the sample flow channel and two of the lateral focusing flow channels are formed;

a second sheet, the second sheet is stacked above the first sheet, and the upper sheet is formed with the upper longitudinal focusing flow passage;

a third sheet, the third sheet is stacked under the first sheet, and the lower sheet is formed with the lower layer longitudinal focusing flow passage;

An upper cover, the upper cover is stacked above the second piece;

a lower cover, the lower cover is stacked under the third piece, and at least one of the upper cover and the lower cover is provided with a focusing flow injection port, and a sample flow communicating with the sample flow inlet An inlet and an outlet connected to the liquid outlet.