Microfluidic device with stable isolation environment

Abstract

The present application provides a microfluidic device, comprising at least one microfluidic channel unit, each microfluidic channel unit comprising a microfluidic channel configured to contain a fluid and comprising a plurality of independent compartments. Each microfluidic channel unit comprises a first side wall and a second side wall opposite and spaced apart from the first side wall, a plurality of first extensions formed on the first side wall extending toward the second side wall without abutting the second side wall, a plurality of second extensions formed on the second side wall extending toward the first side wall without abutting the first side wall, the plurality of first extensions and the plurality of second extensions being alternately arranged in the microfluidic channel. A compartment is formed in at least one first extension or at least one second extension. The compartment has an opening positioned such that the fluid does not directly flow into each compartment. The microfluidic device of the present application has a stable isolated environment to facilitate various reactions and prevent micro-objects in the compartments from escaping.

Description

Technical Field

[0001] This invention relates to microfluidic devices for bioanalysis, and more particularly to microfluidic devices having a stable, isolated environment that facilitates various reactions and prevents the escape of microparticles from the compartment. Background Technology

[0002] With the development of biochip technology, microfluidics, as a key supporting technology for biochips, has received increasing attention. Microfluidic devices are application products of microfluidics technology, which can be used in important application areas such as biomedicine, new drug synthesis and screening, food inspection, and environmental monitoring. In the field of bioanalysis, the applications of microfluidics technology mainly focus on nucleic acid separation and quantification, DNA sequencing, gene mutation, differential gene expression analysis, single-molecule detection, and single-cell analysis. Microfluidics technology can use analytical samples in quantities of only a few microliters to tens of microliters, and the concentration of the analyte can be as low as the picomolar or femtomolar level.

[0003] Microfluidic devices typically include compartments to capture or isolate micro-objects (e.g., cells, microspheres) to facilitate operations such as single-cell capture or detection. For example, CN 109694806 A discloses a microfluidic device including a microfluidic channel with a microchamber at the bottom of the channel's inner lumen for dispensing single cells. Similarly, CN 103894248 B discloses a microfluidic chip including a microfluidic channel with an array of micropores below the channel to accommodate single cells.

[0004] In the aforementioned microfluidic device, the compartments are located below the microfluidic channels to capture cells by gravity and prevent cell escape. However, this arrangement results in a relatively thick microfluidic device, preventing the formation of a compact structure and making it difficult to remove cells from the compartments. Furthermore, even after cells enter, fluid continues to flow directly into the compartments, failing to create a stable isolation environment.

[0005] CN 108070582 B discloses a microfluidic device comprising a fence for biological microtargets. The fence includes a single opening leading to a flow channel and is oriented to a flow path that does not directly face the flow channel, thereby allowing the medium within the fence to diffusely mix with the medium within the flow channel. The microfluidic device is provided with electrodes that generate dielectrophoretic (DEP) forces to manipulate cells within the flow channel and the fence.

[0006] CN 105658781 B discloses a microfluidic device including an isolation fence. The fence includes an isolation region and a connecting region. The connecting region connects a flow channel and the isolation region. Fluid in the flow channel can partially enter the connecting region, while the isolation region is an unaffected region where fluid cannot flow directly into the isolation region.

[0007] In these microfluidic devices, compartments are located on the sides of the microfluidic channel, and micro-objects are moved into or out of the compartments by forces such as DEP. However, in such microfluidic devices, these compartments have relatively complex design and dimensional requirements, which increases the manufacturing difficulties of microfluidic devices.

[0008] CN 207828268 U discloses a microfluidic chip in which a micropore is provided at one end of a droplet-capturing microcavity. When a droplet flows into the droplet-capturing microcavity following the fluid, it blocks the micropore, causing subsequent droplets to move along the side channel, thereby achieving physical isolation of the droplets. However, in this device, the opening of the microcavity faces the direction of fluid flow, causing the droplet to be continuously impacted by the fluid flow after it flows in, making it easy for it to be ejected from the microcavity due to rebound, and it also cannot keep the environment around the isolated droplet stable.

[0009] In view of this, there is a need in the art for an improved microfluidic device to overcome the aforementioned deficiencies in the prior art. Summary of the Invention

[0010] One aspect of the present invention provides a microfluidic device comprising at least one microfluidic channel unit, each microfluidic channel unit including a microfluidic channel configured to contain fluid, and the microfluidic channel comprising a plurality of independent compartments for containing micro-objects. Each microfluidic channel unit includes a first sidewall and a second sidewall opposite to and spaced from the first sidewall, the microfluidic channel being formed between the first sidewall and the second sidewall. A plurality of first extensions extending toward but not abutting the second sidewall are formed on the first sidewall, and a plurality of second extensions extending toward but not abutting the first sidewall are formed on the second sidewall, the plurality of first extensions and the plurality of second extensions being alternately arranged in the microfluidic channel. The compartment is formed in at least one first extension or at least one second extension. The compartment has an opening positioned to prevent the fluid from flowing directly into each compartment.

[0011] In some embodiments, the opening of the compartment is perpendicular to the direction of fluid flow at that opening.

[0012] In some embodiments, the compartment is formed on the side of the first extension and / or the second extension. In some embodiments, the compartment is formed on the same side of the first extension and / or the second extension. In some embodiments, the compartment is formed at the end of the first extension and / or the second extension.

[0013] In some embodiments, at least one of the first extensions or at least one of the second extensions is provided with at least two of the compartments.

[0014] In some embodiments, the compartments in the plurality of first extensions are equidistant from the first sidewall. In some embodiments, the compartments in the plurality of second extensions are equidistant from the second sidewall. In some embodiments, the distance between the compartment and the first sidewall is equal to the distance between the compartment and the second sidewall, that is, the compartment is located in the middle of the microfluidic channel.

[0015] In some embodiments, at least some of the compartments have a rectangular cross-section along the extending direction of the first or second extension. In some embodiments, at least some of the compartments have a square cross-section along the extending direction of the first or second extension. In some embodiments, the cross-section of at least some of the compartments along the extending direction of the first or second extension is a portion of a circle. In some embodiments, the cross-section of at least some of the compartments along the extending direction of the first or second extension is a portion of an ellipse.

[0016] In some embodiments, the first extension and the second extension extend parallel to each other. In some embodiments, the first extension extends perpendicularly from the first sidewall. In some embodiments, the second extension extends perpendicularly from the second sidewall.

[0017] In some embodiments, the first extension and the second extension extend from the first sidewall or the second sidewall by an equal distance. In some embodiments, each of the plurality of first extensions extends from the first sidewall by an equal distance. In some embodiments, each of the plurality of second extensions extends from the second sidewall by an equal distance.

[0018] In some embodiments, the ratio of the distance the first extension extends from the first sidewall to the distance between the first and second sidewalls is about 0.6 to about 0.9. In some embodiments, the ratio of the distance the second extension extends from the second sidewall to the distance between the first and second sidewalls is about 0.6 to about 0.9. In some embodiments, the ratio of the distance between the first extension and the adjacent second extension to the distance between the first and second sidewalls is about 0.2 to about 0.3. In some embodiments, the ratio of the opening width of the compartment to the distance between the first and second sidewalls is about 0.1 to about 0.25. In some embodiments, the ratio of the depth of the compartment to the distance between the first and second sidewalls is about 0.1 to about 0.25. In this invention, the opening width of the compartment is defined as the length of the opening of the compartment extending along the flow direction of the fluid passing through the compartment. In this invention, the depth of the compartment is defined as the length of the compartment extending perpendicular to the flow direction of the fluid passing through the compartment.

[0019] In some embodiments, the distance between the first sidewall and the second sidewall is about 150 to about 250 micrometers. In some embodiments, the first extension extends from the first sidewall by about 120 to about 180 micrometers. In some embodiments, the second extension extends from the second sidewall by about 120 to about 180 micrometers. In some embodiments, the distance between the first extension and the adjacent second extension is about 40 to about 60 micrometers. In some embodiments, the opening width of the compartment is about 20 to about 50 micrometers. In some embodiments, the depth of the compartment is about 20 to about 50 micrometers.

[0020] A second aspect of the present invention provides a microfluidic device comprising at least one microfluidic channel unit, each microfluidic channel unit including a microfluidic channel configured to contain fluid, the microfluidic channel comprising a plurality of independent compartments for containing micro-objects. Each microfluidic channel unit includes a first sidewall, a second sidewall opposite to and spaced apart from the first sidewall, and an intermediate sidewall located between and spaced apart from the first and second sidewalls, wherein the first sidewall and the intermediate sidewall form a first sub-channel of the microfluidic channel, and the second sidewall and the intermediate sidewall form a second sub-channel of the microfluidic channel. A plurality of first extensions extending toward but not abutting the intermediate sidewall are formed on the first sidewall; a plurality of second extensions extending toward but not abutting the intermediate sidewall are formed on the second sidewall; and a plurality of third extensions extending toward but not abutting the first sidewall and a plurality of fourth extensions extending toward but not abutting the second sidewall are formed on the intermediate sidewall. The plurality of first extensions and the plurality of third extensions are arranged alternately in a first sub-channel, and the plurality of second extensions and the plurality of fourth extensions are arranged alternately in a second sub-channel. The compartment is formed in at least one first extension, at least one second extension, at least one third extension, and at least one fourth extension. The compartment has an opening positioned to prevent the fluid from flowing directly into each compartment.

[0021] In some embodiments, a diverter is provided on the intermediate sidewall, the diverter being configured to guide fluid into the first sub-channel and the second sub-channel, respectively. In a further embodiment, the diverter is a protrusion located at the end of the intermediate sidewall.

[0022] In some embodiments, the first sub-channel and the second sub-channel have a common fluid inlet and a fluid outlet. In some embodiments, the microfluidic device includes a plurality of microfluidic channel units, the plurality of microfluidic channel units having a common fluid inlet and a fluid outlet.

[0023] In this invention, a series of opposing and alternating extensions are formed in the microfluidic channel. These extensions can change the flow direction of the fluid, so that when the fluid flows in the microfluidic channel, it forms a continuously tortuous, non-linear fluid flow, thereby creating a specific velocity distribution. Furthermore, the opening of the compartment is positioned so that the fluid does not flow directly into the compartment, but can only enter the compartment by diffusion, thereby providing a stable fluid environment for the isolated micro-objects, facilitating various reactions (e.g., the reaction of cell secretions with subsequently added reagents), and preventing the micro-objects from escaping the compartment. Attached Figure Description

[0024] This invention will be described in more detail with reference to the accompanying drawings. It should be noted that the illustrated schemes are merely representative examples of embodiments of the invention, and to more clearly illustrate the details of exemplary embodiments, the elements in the drawings are not drawn to scale; the number of actual elements may vary, the relative positions of the actual elements remain substantially consistent with the illustrations, and some elements are not shown. In cases where multiple embodiments exist, when one or more features described in previous embodiments are also applicable to another embodiment, for the sake of brevity, these reusable features will not be repeated in subsequent embodiments. These subsequent embodiments should be understood as having described these reusable features, unless otherwise stated. Those skilled in the art will recognize upon reading this invention that one or more features shown in one figure can be combined with one or more features in another figure to construct one or more alternative embodiments not specifically shown in the drawings, and these alternative embodiments also constitute a part of this invention.

[0025] Figure 1 This diagram shows a microfluidic channel unit included in a microfluidic device according to an embodiment of the present invention.

[0026] Figure 2 show Figure 1 A magnified view of a microfluidic channel unit.

[0027] Figure 3 show Figure 2 The local velocity distribution of the microfluidic channel unit.

[0028] Figure 4 show Figure 1 A schematic diagram showing the variations of the microfluidic channel unit.

[0029] Figure 5 show Figure 1 A partial schematic diagram of another variation of the microfluidic channel unit shown.

[0030] Figure 6A schematic diagram showing a microfluidic channel unit included in a microfluidic device according to another embodiment of the present invention is shown.

[0031] Figure 7 show Figure 6 The velocity distribution diagram of the microfluidic channel unit.

[0032] Figure 8 show Figure 6 The simulation results of the microsphere distribution in the software for the microfluidic channel unit are shown.

[0033] Figure 9 show Figure 6 Another simulation result of the microsphere distribution in the software for the microfluidic channel unit shown.

[0034] Figure 10 The results show real-world test results using the microfluidic channel unit of the present invention, in which cells never entered the compartment.

[0035] Figure 11 The results show real-world test results using the microfluidic channel unit of the present invention, in which the cells never left the compartment.

[0036] Figure 12 A schematic diagram of a microfluidic device according to another embodiment of the present invention is shown, which includes a plurality of microfluidic channel units.

[0037] The meanings of the reference numerals in the attached figures are summarized as follows. Reference numerals with the same numbers represent the same elements. 100, 200, 320, 340, 360 - Microfluidic channel unit; 102, 202 - First sidewall; 104, 204 - Second sidewall; 203 - Intermediate sidewall; 106, 206 - First extension; 108, 208 - Second extension; 207 - Third extension; 209 - Fourth extension; 110, 110a, 110b, 110c - Compartment; 120 - Baffle; 212, 214 - Sub-channel; 205 - Diverter; L0, L1, L2, L3, w, d indicate dimensions; Arrows D, D1, D2, D3, F, F', F1', F2', F3' indicate direction. Detailed Implementation

[0038] The exemplary embodiments of the present invention are described in detail below with reference to the accompanying drawings. It should be understood that the scope of the present invention is not limited to the disclosed embodiments. Those skilled in the art, after reading the disclosure of this invention, can modify and vary these exemplary embodiments based on the teachings of the present invention, without any inventive effort. Such modifications and variations are intended to be included within the scope outlined in the appended claims.

[0039] refer to Figure 1 The illustration schematically shows one of the microfluidic channel units 100 included in a microfluidic device according to an embodiment of the present invention. The microfluidic channel unit 100 includes a first sidewall 102 and a second sidewall 104 opposite to and spaced apart from the first sidewall 102. A microfluidic channel is formed between the first sidewall 102 and the second sidewall 104. Fluid flows in from one end of the microfluidic channel unit 100 in the direction indicated by arrow F, then flows between the first sidewall 102 and the second sidewall 104, and finally flows out from the other end of the microfluidic channel unit 100.

[0040] A plurality of first extensions 106 extending toward the second sidewall 104 are formed on the first sidewall 102. A plurality of second extensions 108 extending toward the first sidewall 102 are formed on the second sidewall 104. The first extensions 106 and the second extensions 108 are arranged alternately in the microfluidic channel. The first extensions 106 extend from the first sidewall 102 but do not abut against the second sidewall 104, thereby changing the flow direction of the fluid. The second extensions 108 extend from the second sidewall 104 but do not abut against the first sidewall 102, thereby again changing the flow direction of the fluid. The first extensions 106 are spaced apart from the adjacent second extensions 108 to form a flow channel for the fluid to flow between the first extensions 106 and the adjacent second extensions 108. When the fluid flows between the first sidewall 102 and the second sidewall 104, it flows alternately through the first extensions 106 and the second extensions 108 in sequence, thereby continuously having its flow direction changed by the first extensions 106 and the second extensions 108 (e.g., direction F').

[0041] like Figure 2 As shown, compartments 110 configured to accommodate micro-objects (e.g., cells, microspheres) are formed on the first extension 106 and the second extension 108. Each compartment 110 has an opening to allow the micro-objects to enter. The compartment 110 extends from this opening to form a cavity, thereby accommodating the micro-objects. Each compartment has only one opening, allowing fluid or micro-objects in the fluid to enter or exit the compartment only through this opening. The openings of the compartments 110 are positioned to prevent direct flow of fluid into each compartment 110. In this embodiment, the opening direction D of the compartment 110 is perpendicular to the fluid flow direction F' at the opening.

[0042] Figure 3 Showing Figure 2The software simulation results of the local velocity distribution of the microfluidic channel unit are shown. It can be seen that the fluid cannot flow directly into the compartment; it can only diffuse a short distance inward from the compartment opening (the maximum diffusion distance in the figure is approximately 10 micrometers). This ensures that the main part of the compartment, not near the opening, is unaffected by fluid flow (the velocity is essentially zero). Therefore, micro-objects (e.g., single cells) inside the compartment, after being introduced into the compartment by, for example, DEP force, are in a stable environment unaffected by fluid flow, and are not impacted or carried by the fluid, thus preventing them from escaping the compartment. This facilitates various reactions within the compartment.

[0043] The first sidewall 102 and the second sidewall 104 preferably extend parallel to each other, or substantially parallel to each other. In other embodiments, the first sidewall 102 and the second sidewall 104 may not extend parallel to each other. A plurality of first extensions 106 and / or a plurality of second extensions 108 may extend in a parallel or non-parallel manner, but are preferably parallel to each other. Figure 1 In the illustrated embodiment, a plurality of first extensions 106 extend vertically from a first sidewall 102, and a plurality of second extensions 108 extend vertically from a second sidewall 104. The distance by which the plurality of first extensions 106 extend from the first sidewall 102 is substantially equal to the distance by which the plurality of second extensions 108 extend from the second sidewall 104.

[0044] In this embodiment, a compartment 110 is formed on one side of the first extension 106 and the second extension 108. Each first extension 106 and each second extension 108 is provided with a compartment 110. In this embodiment, the compartment 110 has a rectangular cross-section along the extending direction of the first or second extension. The distance between the compartment 110 and the first sidewall 102 is substantially equal to the distance between the compartment 110 and the second sidewall 104, such that the compartment is located substantially in the middle of the microfluidic channel. This arrangement allows for rapid determination of the compartment's location, facilitating observation.

[0045] Figure 1 The fluid flows in from the left and out from the right, with its overall flow direction F being the same as the direction of the compartment opening. However, the overall flow direction of the fluid in the microfluidic channel unit of the present invention is not limited to this embodiment. For example, Figure 4 Showing Figure 1 The illustrated variation of the microfluidic channel unit shows fluid flowing in from the right and out from the left, with the overall flow direction F opposite to the direction of the compartment opening. As a preferred feature, in Figure 4 In the microfluidic channel, a baffle 120 may be provided at the fluid inlet to prevent fluid from flowing directly into the first compartment (shown by an arrow) along the fluid flow direction.

[0046] Figure 5 show Figure 1A partial schematic diagram of another variation of the microfluidic channel unit shown. Chambers 110a and 110b are respectively provided on both sides of the first extension 106, and chamber 110c is provided at the end of the second extension 108. The opening directions D1, D2, and D3 of chambers 110a, 110b, and 110c are perpendicular to the fluid flow directions F1', F2', and F3' at the openings, respectively. In other embodiments, the chambers may be located at other positions of the extension. In this embodiment, chamber 110a has a square cross-section along the extension direction of the first or second extension, chamber 110b has a portion of a circle in cross-section, and chamber 110c has a portion of an ellipse in cross-section. In other embodiments, the chambers may have cross-sectional shapes of other shapes. Chambers with different shapes and sizes can accommodate different micro-objects. The first extension 106 has two chambers 110a and 110b. The two chambers 110a and 110b are respectively located on both sides of the first extension 106. In other embodiments, the two compartments 110a and 110b may be located on the same side of the first extension 106.

[0047] refer to Figure 2 The example shows the specific dimensional relationships between the various components.

[0048] The distance L0 between the first sidewall 102 and the second sidewall 104 can be approximately 150 to approximately 250 micrometers, for example, approximately 160 to approximately 240 micrometers, or approximately 170 to approximately 230 micrometers, or approximately 180 to approximately 220 micrometers, or approximately 190 to approximately 210 micrometers, or approximately 200 micrometers. In this embodiment, the distance L0 between the first sidewall 102 and the second sidewall 104 is 200 micrometers.

[0049] The ratio of the distance L1 from the first extension 106 extending from the first sidewall 102 or the distance L2 from the second extension 108 extending from the second sidewall 104 to the distance L0 between the first sidewall 102 and the second sidewall 104 can be from about 0.6 to about 0.9, for example, from about 0.65 to about 0.85, or from about 0.7 to about 0.8, or about 0.75. In this embodiment, the ratio of the distance L1 from the first extension 106 extending from the first sidewall 102 or the distance L2 from the second extension 108 extending from the second sidewall 104 to the distance L0 between the first sidewall 102 and the second sidewall 104 is 0.75. For example, the distance L1 from the first extension 106 extending from the first sidewall 102 or the distance L2 from the second extension 108 extending from the second sidewall 104 can be from about 120 to about 180 micrometers, for example, from about 130 to about 170 micrometers, or from about 140 to about 160 micrometers, or about 150 micrometers. In this embodiment, the distance L1 from which the first extension 106 extends from the first sidewall 104 and the distance L2 from which the second extension 108 extends from the second sidewall 104 are both 150 micrometers.

[0050] The ratio of the distance L3 between the first extension 106 and the adjacent second extension 108 to the distance L0 between the first sidewall 102 and the second sidewall 104 can be from about 0.2 to about 0.3, for example, about 0.25. In this embodiment, the ratio of the distance L3 between the first extension 106 and the adjacent second extension 108 to the distance L0 between the first sidewall 102 and the second sidewall 104 is 0.25. For example, the distance L3 between the first extension 106 and the adjacent second extension 108 is from about 40 to about 60 micrometers, for example, from about 45 to 55 micrometers, for example, about 50 micrometers. In this embodiment, the distance between the first extension 106 and the adjacent second extension 108 is 50 micrometers.

[0051] The length of the opening of compartment 110 extending along the flow direction of the fluid passing through compartment 110 forms the opening width w of compartment 110. The ratio of the opening width w of compartment 110 to the distance L0 between the first sidewall 102 and the second sidewall 104 can be from about 0.1 to about 0.25, for example from about 0.125 to about 0.225, or from about 0.15 to about 0.2. In this embodiment, the ratio of the opening width w of compartment 110 to the distance L0 between the first sidewall 102 and the second sidewall 104 is 0.18. For example, the opening width w of compartment 110 can be from about 20 to about 50 micrometers, for example from about 25 to about 45 micrometers, or from about 30 to about 40 micrometers. In this embodiment, the opening width w of compartment 110 is 36 micrometers.

[0052] The compartment 110 extends inward from the opening to a depth d. The ratio of the depth d of the compartment 110 to the distance L0 between the first sidewall 102 and the second sidewall 104 can be from about 0.1 to about 0.25, for example, from about 0.125 to about 0.225, or from about 0.15 to about 0.2. In this embodiment, the ratio of the depth d of the compartment 110 to the distance L0 between the first sidewall 102 and the second sidewall 104 is 0.175. For example, the depth d of the compartment 110 can be from about 20 to about 50 micrometers, for example, from about 25 to about 45 micrometers, or from about 30 to about 40 micrometers. In this embodiment, the depth d of the compartment 110 is 35 micrometers.

[0053] In some implementations, the size of the compartments is configured to accommodate a single cell, for example, a single cell with a diameter of about 20 to 30 micrometers.

[0054] Figure 6 The illustration schematically shows a microfluidic channel unit 200 included in a microfluidic device according to another embodiment of the present invention. Figure 1Similar to the microfluidic channel unit 100 shown, the microfluidic channel unit 200 includes a first sidewall 202 and a second sidewall 204. A microfluidic channel is formed between the first sidewall 202 and the second sidewall 204. Fluid flows in from one end of the microfluidic channel unit 200 in the direction indicated by arrow F, then flows between the first sidewall 202 and the second sidewall 204, and finally flows out from the other end of the microfluidic channel unit 200.

[0055] The microfluidic channel unit 200 further includes an intermediate sidewall 203 located between the first sidewall 202 and the second sidewall 204. The intermediate sidewall 203 divides the microfluidic channel into two sub-channels: a first sub-channel 212 formed by the first sidewall 202 and the intermediate sidewall 203, and a second sub-channel 214 formed by the second sidewall 204 and the intermediate sidewall 203. A protrusion 205 is provided on the end of the intermediate sidewall 203 adjacent to the fluid inlet, which guides fluid into the first sub-channel 212 and the second sub-channel 214, respectively.

[0056] A plurality of first extensions 206 extending toward the intermediate sidewall 203 are formed on the first sidewall 202, and a plurality of third extensions 207 extending toward the first sidewall 202 are formed on the intermediate sidewall 203. The first extensions 206 and third extensions 207 are arranged alternately in the first sub-channel 212. A plurality of second extensions 208 extending toward the intermediate sidewall 203 are formed on the second sidewall 204, and a plurality of fourth extensions 209 extending toward the second sidewall 204 are formed on the intermediate sidewall 203. The second extensions 208 and fourth extensions 209 are arranged alternately in the second sub-channel 214. Each of the first extensions 206, second extensions 208, third extensions 207, and fourth extensions 209 has a compartment configured to accommodate micro-objects. The opening direction of the compartment is perpendicular to the flow direction of the fluid at the opening.

[0057] The first sub-channel 212 and the second sub-channel 214 are connected to Figure 1 The microfluidic channel unit 100 is formed in essentially the same manner. When the fluid flows in the first sub-channel 212 and the second sub-channel 214, it flows alternately through the extensions therein, thereby constantly changing the flow direction and forming a specific flow velocity distribution. Figure 7 The software simulation results of the flow velocity distribution of the microfluidic channel unit 200 are shown. It can be seen that there is no significant fluid flow in any of the compartments, forming a stable isolation environment that facilitates various chemical or biological reactions within the compartments and prevents micro-objects within the compartments from escaping after being introduced by, for example, DEP forces.

[0058] Figure 8 and 9 Showing the use of software simulation in Figure 7The motion of microspheres within the microfluidic channel unit 200 is shown. Simulation conditions were set using COMSOL 5.5 software as follows: Left inlet velocity: 1 mm / s; Direction: Left to right; Right side: Atmospheric pressure; Simulated liquid: Water; Microsphere diameter: 20 μm; Condition upon wall contact: Stick.

[0059] Figure 8 A shows that the microspheres are moved into the compartments at second 0, so that all compartments contain microspheres in this initial state. Then, the fluid flow is simulated according to the simulation conditions described above. Figure 8 Figures B and 8C show the situation after 50 seconds and 100 seconds of fluid flow, respectively. As can be seen from the figures, although the microspheres move slightly within the compartment due to the effect of fluid diffusion, they only move to the edge of the compartment at most. No microspheres are able to escape the compartment, and all microspheres remain inside the compartment.

[0060] Figure 9 A shows that microspheres are injected from the left inlet at second 0, at which point the microspheres accumulate at the left inlet, and none of the compartments contain microspheres. Fluid flow is then simulated under the same conditions. Figure 9 Figure B shows the situation after 50 seconds of fluid flow. As can be seen from the figure, without additional force, all microspheres flowed to and accumulated at the outlet on the right, except for a few microspheres that adhered to the bend; no microspheres flowed into the compartment. A total of 8 injections were performed, and the simulation results were consistent across all simulations.

[0061] Figure 10 and 11 The microfluidic channel unit of the present invention was demonstrated in a practical experiment, and the microfluidic channel unit is compared with... Figure 1 The microfluidic channel units 100 are similarly formed. Figure 10 The figures show the flow of cell-containing fluid within a microfluidic channel unit for 0, 5, 10, and 15 seconds, with none of the compartments containing cells at 0 seconds. As can be seen from the figures, cells do not flow into any of the compartments as the fluid flows. Figure 11 The flow of cell-containing fluid within a microfluidic channel unit was shown for 0, 5, 10, and 12 seconds, respectively. Figure 10 The difference is that at second 0, there are two compartments, each containing one cell (as indicated by the arrows, moved in by DEP force). As can be seen from the diagram, the cells in the compartments are not washed away by the fluid and remain in the compartments. Figure 10 and 11 Confirmed with Figure 8 and 9The consistent result is that a space unaffected by fluid flow is formed within the compartment, preventing micro-objects in the fluid from flowing into the compartment without external forces, while micro-objects already in the compartment are not flushed out by the fluid. Similar results were obtained by varying the fluid velocity between 0 and 5 mm / s.

[0062] Figure 12 A microfluidic device according to another embodiment of the present invention is schematically illustrated, comprising a first microfluidic channel unit 320, a second microfluidic channel unit 340, and a third microfluidic channel unit 360. The first microfluidic channel unit 320, the second microfluidic channel unit 340, and the third microfluidic channel unit 360 are all formed having a... Figure 7 The microfluidic channel unit 200 shown has the same structure. The three microfluidic channel units are arranged in parallel and have a common fluid inlet.

[0063] Those skilled in the art will readily understand that microfluidic devices may include more or fewer microfluidic channel units. These microfluidic channel units may be connected in parallel, in series, or otherwise arranged. Each microfluidic channel unit may have the same or different microfluidic channels. Each microfluidic channel unit may have 50 to 100 compartments, and repeated arrangements can result in a microfluidic device with up to 7,500 compartments or more.

[0064] This invention only describes in detail the characteristics of the microfluidic channels in the microfluidic device. Other components that may be present in the microfluidic device, such as control systems, optical pattern generation systems, image acquisition systems, and optical tweezers, are not particularly limited in this invention and can be configured accordingly with reference to existing technologies.

[0065] The above descriptions are representative examples of embodiments of the present invention and are provided for illustrative purposes only. The present invention contemplates that one or more technical features used in one embodiment can be added to another embodiment to form improved or alternative embodiments without departing from the purpose of the embodiment. Similarly, one or more technical features used in one embodiment can be omitted or replaced without departing from the purpose of the embodiment to form alternative or simplified embodiments. Furthermore, one or more technical features used in one embodiment can be combined with one or more technical features in another embodiment without departing from the purpose of the embodiment to form improved or alternative embodiments. The present invention is intended to include all of the above-mentioned improved, alternative, and simplified technical solutions.

Claims

1. A microfluidic device comprising at least one microfluidic channel unit, each microfluidic channel unit including a microfluidic channel configured to contain fluid, and the microfluidic channel comprising a plurality of independent compartments for containing micro-objects, characterized in that, Each of the microfluidic channel units includes a first sidewall and a second sidewall opposite to and spaced apart from the first sidewall, wherein the microfluidic channel is formed between the first sidewall and the second sidewall. The first sidewall has a plurality of first extensions extending toward but not abutting the second sidewall, and the second sidewall has a plurality of second extensions extending toward but not abutting the first sidewall. The plurality of first extensions and the plurality of second extensions are arranged alternately in the microfluidic channel. The compartment is formed in at least one of the first extensions or at least one of the second extensions. The compartment has an opening that is positioned to prevent the fluid from flowing directly into each compartment.

2. The microfluidic device according to claim 1, characterized in that, The opening of the compartment is perpendicular to the direction of fluid flow at that opening.

3. The microfluidic device according to claim 1, characterized in that, The compartment is formed on the side of the first extension and / or the second extension.

4. The microfluidic device according to claim 1, characterized in that, The compartment is formed on the same side of the first extension and / or the second extension.

5. The microfluidic device according to claim 1, characterized in that, The compartment is formed at the end of the first extension and / or the second extension.

6. The microfluidic device according to claim 1, characterized in that, At least one of the first extensions or at least one of the second extensions is provided with at least two of the compartments.

7. The microfluidic device according to claim 1, characterized in that, The compartments in the plurality of first extensions are equidistant from the first sidewall, and the compartments in the plurality of second extensions are equidistant from the second sidewall.

8. The microfluidic device according to claim 1, characterized in that, The distance between the compartment and the first side wall is equal to the distance between the compartment and the second side wall.

9. The microfluidic device according to claim 1, characterized in that, The cross-section of the compartment along the extending direction of the first or second extension is rectangular, square, a portion of a circle, or a portion of an ellipse.

10. The microfluidic device according to claim 1, characterized in that, The first extension and the second extension extend parallel to each other.

11. The microfluidic device according to claim 1, characterized in that, The first extension extends vertically from the first sidewall, and the second extension extends vertically from the second sidewall.

12. The microfluidic device according to claim 1, characterized in that, The first extension and the second extension extend from the first sidewall or the second sidewall by an equal distance.

13. The microfluidic device according to any one of claims 1 to 12, characterized in that, The ratio of the distance the first extension extends from the first sidewall and / or the distance the second extension extends from the second sidewall to the distance between the first sidewall and the second sidewall is 0.6 to 0.

9.

14. The microfluidic device according to any one of claims 1 to 12, characterized in that, The ratio of the distance between the first extension and the adjacent second extension to the distance between the first sidewall and the second sidewall is 0.2 to 0.

3.

15. The microfluidic device according to any one of claims 1 to 12, characterized in that, The ratio of the opening width of the compartment to the distance between the first and second side walls is 0.1 to 0.

25.

16. The microfluidic device according to any one of claims 1 to 12, characterized in that, The ratio of the depth of the compartment to the distance between the first and second sidewalls is 0.1 to 0.

25.

17. The microfluidic device according to claim 13, characterized in that, The distance between the first and second sidewalls is 150 to 250 micrometers.

18. The microfluidic device according to claim 17, characterized in that, The distance by which the first extension extends from the first sidewall and / or the distance by which the second extension extends from the second sidewall is 120 to 180 micrometers.

19. The microfluidic device according to claim 17, characterized in that, The distance between the first extension and the adjacent second extension is 40 to 60 micrometers.

20. The microfluidic device according to claim 17, characterized in that, The opening width of the compartment is 20 to 50 micrometers.

21. The microfluidic device according to claim 17, characterized in that, The depth of the compartment is 20 to 50 micrometers.

22. A microfluidic device comprising at least one microfluidic channel unit, each microfluidic channel unit including a microfluidic channel configured to contain fluid, the microfluidic channel comprising a plurality of independent compartments for containing micro-objects, characterized in that, Each of the microfluidic channel units includes a first sidewall, a second sidewall opposite to and spaced apart from the first sidewall, and an intermediate sidewall located between and spaced apart from the first and second sidewalls, wherein the first sidewall and the intermediate sidewall form a first sub-channel of the microfluidic channel, and the second sidewall and the intermediate sidewall form a second sub-channel of the microfluidic channel. The first sidewall has a plurality of first extension portions that extend toward but do not abut against the middle sidewall; the second sidewall has a plurality of second extension portions that extend toward but do not abut against the middle sidewall; and the middle sidewall has a plurality of third extension portions that extend toward but do not abut against the first sidewall and a plurality of fourth extension portions that extend toward but do not abut against the second sidewall. The plurality of first extensions and the plurality of third extensions are arranged alternately in the first sub-channel, and the plurality of second extensions and the plurality of fourth extensions are arranged alternately in the second sub-channel. The compartment is formed in at least one first extension, at least one second extension, at least one third extension, and at least one fourth extension. The compartment has an opening that is positioned to prevent the fluid from flowing directly into each compartment.

23. The microfluidic device according to claim 22, characterized in that, A flow divider is provided on the middle sidewall, which is configured to guide fluid into the first sub-channel and the second sub-channel respectively.

24. The microfluidic device according to claim 23, characterized in that, The diverter is a protrusion located at the end of the intermediate sidewall.

25. The microfluidic device according to claim 22, characterized in that, The first sub-channel and the second sub-channel have a common fluid inlet and fluid outlet.

26. The microfluidic device according to claim 22, characterized in that, The microfluidic device includes a plurality of microfluidic channel units, which have a common fluid inlet and fluid outlet.

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