Microfluidic chips and microfluidic devices with annular reaction channels
By using capillary pumps and photodeformable materials to drive microfluidics, the problems of complex structure and high sample loss in traditional microfluidic chips are solved, enabling self-driven measurement of micro-samples and portable design.
Patent Information
- Application Number
- CN202310511050.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Patents(China)
- Current Assignee / Owner
- Filing Date
- 2023-05-08
- Publication Date
- 2025-12-02
- Estimated Expiration
- 2043-05-08
AI Technical Summary
Traditional microfluidic chips require external power pump and valve components to drive the fluid, which is complex in structure, cumbersome in operation, difficult to make portable, and has a large sample loss, making it impossible to achieve true micro-sample measurement.
A capillary pump is used to generate a Laplace pressure difference to drive the fluid. Combined with annularly arranged reaction channels and photodeformable materials, the pressure difference generated by asymmetric photodeformation enables the microfluidic to be self-driven in the microfluidic chip, avoiding the need for external power pump and valve components.
It enables contactless measurement of micro-samples, reduces the requirements for fluid continuity, reduces sample loss, and simplifies the structure, making it suitable for portable applications.
Smart Images

Figure CN116474850B_ABST
Abstract
Description
Technical Field
[0001] This disclosure relates to the field of microfluidics, and more specifically, to a microfluidic chip and its operating method, a microfluidic device, and a microfluidic equipment. Background Technology
[0002] Microfluidics integrates complex microfluidic operations such as sample preparation, reaction, separation, and detection in biological, chemical, and medical analyses onto a single chip of a few square centimeters, enabling automated completion of the entire analytical process. It offers advantages such as high integration and high throughput. Traditional microfluidic chips require complex fluid channels and externally powered pumps and valves to drive and control fluid movement, resulting in complex structures, cumbersome operation, and difficulty in portability. Furthermore, the continuous flow of fluid driven by these pumps and valves requires filling the entire upstream channel before the final measurement operation, leading to significant sample loss. Therefore, current microfluidic chips based on externally powered pumps and valves cannot yet achieve truly effective measurement of minute samples. Summary of the Invention
[0003] A brief overview of this disclosure is given below to provide a basic understanding of some aspects of it. However, it should be understood that this overview is not an exhaustive summary of this disclosure. It is not intended to identify key or essential parts of this disclosure, nor is it intended to limit the scope of this disclosure. Its purpose is merely to present certain concepts of this disclosure in a simplified form as a prelude to the more detailed description that follows.
[0004] According to one aspect of this disclosure, a microfluidic chip is provided, the microfluidic chip including a microfluidic unit, the microfluidic unit including: an inlet configured to receive sample microfluidic fluid; an inlet channel configured to communicate with the inlet to receive sample microfluidic fluid from the inlet; a capillary pump configured to communicate with the inlet channel to draw sample microfluidic fluid through and out of the inlet channel; and one or more reaction units, each reaction unit including: a reaction channel arranged in a ring, configured to communicate with the inlet channel via a dispensing channel corresponding to the reaction unit between the inlet and the capillary pump to receive a preset volume of sample microfluidic fluid corresponding to the reaction unit from the inlet channel, wherein the reaction channel includes a photodeformable material that allows the microfluidic fluid to be... Driven by the Laplace pressure difference generated by the asymmetric photoinduced deformation of the reaction channel, the sample microfluidic fluid is driven through the reaction channel. The first connecting structure is configured to be connected to the reaction channel at one end and kept connected to the atmosphere at the other end, so that the sample microfluidic fluid can self-close the first connecting structure after entering the first connecting structure from the sample dispensing channel through the reaction channel. The first connection point of the sample dispensing channel and the reaction channel and the second connection point of the reaction channel and the first connecting structure are spaced apart from each other along the longitudinal centerline of the reaction channel. The cross-sectional area of the sample injection channel is larger than that of the reaction channel, the cross-sectional area of the reaction channel is larger than that of the first connecting structure, the cross-sectional area of the reaction channel is larger than that of the sample dispensing channel, and the depth of the reaction channel is greater than that of the sample dispensing channel.
[0005] According to another aspect of this disclosure, a microfluidic device is provided, comprising a microfluidic chip as described in embodiments of this disclosure and a light source configured to provide illumination to the microfluidic chip to control the movement of microfluidics within the microfluidic chip.
[0006] According to another aspect of this disclosure, a microfluidic device is provided, comprising: a light control module including a light source configured to provide illumination to a microfluidic chip to control the movement of microfluidics in the microfluidic chip, the microfluidics in the microfluidic chip being photoactuable; and a movement module configured to move the microfluidic chip to adjust the relative position of the microfluidic chip and the light source, such that the microfluidic chip is selectively and locally illuminated by the light source, thereby photoactuating the microfluidics in the microfluidic chip, wherein the light control module is fixed above the movement module.
[0007] Other features and advantages of this disclosure will become clearer from the following detailed description of exemplary embodiments with reference to the accompanying drawings. Attached Figure Description
[0008] The accompanying drawings, which form part of this specification, illustrate embodiments of the present disclosure and, together with the specification, serve to explain the principles of the disclosure. The embodiments set forth in the drawings are illustrative and exemplary in nature and are not intended to limit the scope of the disclosure. The following detailed description of exemplary embodiments will be clearly understood when read in conjunction with the following drawings, wherein similar structures are indicated by similar reference numerals, and wherein:
[0009] Figures 1 to 5 This is a schematic diagram illustrating a microfluidic chip according to some embodiments of the present disclosure;
[0010] Figure 6 This is a schematic diagram illustrating a non-limiting example process of photo-driven microfluidics in a microfluidic chip according to an embodiment of the present disclosure;
[0011] Figure 7 and Figure 8 This is a flowchart illustrating a method of operating a microfluidic chip according to some embodiments of the present disclosure;
[0012] Figures 9 to 13 This is a schematic diagram illustrating a microfluidic device according to some embodiments of the present disclosure;
[0013] Figure 14 This is a schematic diagram illustrating a microfluidic device according to some embodiments of the present disclosure;
[0014] Figure 15 It is shown Figure 14 A schematic diagram of the moving module of the microfluidic device shown;
[0015] Figure 16 It is shown Figure 14 A schematic diagram of the light control module of the microfluidic device shown. Detailed Implementation
[0016] Various exemplary embodiments of the present disclosure will now be described in detail with reference to the accompanying drawings. It should be noted that, unless otherwise specifically stated, the relative arrangement, numerical expressions, and values of the components and steps set forth in these embodiments do not limit the scope of the present disclosure.
[0017] The following description of at least one exemplary embodiment is merely illustrative and is in no way intended to limit the scope of this disclosure or its application or use. That is, the structures and methods herein are shown in an exemplary manner to illustrate different embodiments of the structures and methods in this disclosure. However, those skilled in the art will understand that they merely illustrate exemplary ways that can be used to implement this disclosure, and not exhaustive ways. Furthermore, the drawings are not necessarily drawn to scale, and some features may be enlarged to show details of specific components.
[0018] In addition, techniques, methods and equipment known to those skilled in the art may not be discussed in detail, but where appropriate, such techniques, methods and equipment should be considered part of the specification.
[0019] In all examples shown and discussed herein, any specific values should be interpreted as merely exemplary and not as limitations. Therefore, other examples of exemplary embodiments may have different values.
[0020] This disclosure provides a microfluidic chip that can drive fluid through a Laplace pressure differential (capillary force) generated by a capillary pump, thereby enabling contactless measurement of micro-samples. Since the microfluidic chip according to this disclosure does not require an externally powered pump-valve assembly to drive the fluid, it has low requirements for fluid continuity, low sample loss, and a small number of components and overall size for the microfluidic chip and its associated equipment. The microfluidic chip according to various embodiments of this disclosure will now be described in detail with reference to the accompanying drawings. It should be understood that actual microfluidic chips may include other components, but to avoid obscuring the key points of this disclosure, these other components will not be discussed herein and are not shown in the drawings. It should also be understood that various embodiments can be combined with each other, but for the sake of brevity, the drawings only exemplarily illustrate some combinations of these embodiments.
[0021] Figure 1 A microfluidic chip 100 according to some embodiments of the present disclosure is shown. For example... Figure 1 As shown, the microfluidic chip 100 includes a microfluidic unit 100U, which includes an inlet 101, an inlet channel 102, a capillary pump 103, and reaction units 110A-110B. It should be understood that although... Figure 1 Two reaction units are shown, but this is merely exemplary and not limiting. The microfluidic chip 100 may include one, two, three or more reaction units as needed.
[0022] Inlet 101 is configured to receive sample microfluidics. Inlet channel 102 is configured to communicate with inlet 101 to receive sample microfluidics from inlet 101. For example, sample microfluidics can be dropped into inlet 101 to fill it, and then extend a distance into inlet channel 102. In this document, cross-section refers to a plane containing the width and depth, perpendicular to the direction of length. Figures 1 to 5The planes shown in the diagrams are the planes containing the width and length, but it should be noted that these diagrams are provided for illustrative purposes and are not necessarily drawn to scale. In some embodiments, the cross-sectional area of the inlet 101 may be greater than or equal to the cross-sectional area of the inlet channel 102. This can facilitate the spontaneous entry of sample microfluidics from the inlet 101 into the inlet channel 102. It should be understood that this disclosure is not limited to adding sample microfluidics to the inlet 101. In some embodiments, the inlet 101 may also be connected to other channels, cavities, etc., on the microfluidic chip 100 to receive sample microfluidics therefrom. For example, the inlet 101 may be connected to a pre-reaction unit to receive sample microfluidics that require further processing after the reaction.
[0023] Capillary pump 103 is configured to communicate with sample inlet channel 102 to draw sample microfluidic fluid through and out of sample inlet channel 102. Capillary pump 103 may generally consist of a combination of multiple capillary channels, each with a cross-sectional area much smaller than the cross-sectional area of the individual channels of microfluidic chip 100, and the ends of these capillary channels are configured to be open to the atmosphere. Therefore, after sample microfluidic fluid enters sample inlet channel 102, it is driven through sample inlet channel 102 by the Laplace pressure difference generated by capillary pump 103 and ultimately drawn away by capillary pump 103. In some embodiments, such as... Figure 1 As shown, the capillary pump 103 may include multiple microchannels arranged in a tree-like pattern. This structure can effectively increase the capillary force generated by the capillary pump on the one hand, and increase the amount of liquid that the capillary pump can hold on the other hand, further improving the utilization rate of the microfluidic chip 100. It should be understood that the illustrated structure of the capillary pump 103 is merely for providing an illustrative example and is not intended to limit this disclosure.
[0024] Each reaction unit includes a reaction channel and a first connecting structure. The reaction channels are arranged in a ring. In this document, the ring only requires that the channels be connected end-to-end; there are no restrictions on the channel outline. The outline of the ring channel can be various suitable shapes, such as polygons (triangles, quadrilaterals, pentagons), circles, ellipses, etc. For example, in the accompanying drawings, the outline of the ring reaction channel is non-limitingly illustrated as a rectangle. The reaction channel is configured to communicate with the injection channel via a dispensing channel corresponding to the reaction unit between the inlet and the capillary pump to receive a predetermined volume of sample microfluidic fluid corresponding to the reaction unit from the injection channel. The reaction channel includes a photodeformable material that allows the microfluidic fluid to be driven (also referred to herein as photodriven) through the reaction channel (to be combined later with...) by the Laplace pressure difference generated by the asymmetric photodeformation of the reaction channel. Figure 6(The process of photo-driven microfluidics described in this paper is described in detail.) The first connecting structure is configured to communicate with the reaction channel at one end and remain open to the atmosphere at the other end, allowing the sample microfluidic to self-close the first connecting structure after entering it from the sample dispensing channel via the reaction channel. The first connection point between the sample dispensing channel and the reaction channel and the second connection point between the reaction channel and the first connecting structure are spaced apart from each other along the longitudinal centerline of the reaction channel. The longitudinal centerline of the reaction channel is a line passing through the center of each cross-section of the reaction channel along its length. It should be understood that, in this paper, the distance between one point and another, as well as the points of symmetry of one point with respect to another, mentioned later, can be considered by imagining the annular reaction channel unfolded into a straight line.
[0025] For example, such as Figure 1 As shown, reaction unit 110A includes a reaction channel 1041 arranged in a ring. Reaction channel 1041 is configured to communicate with injection channel 102 via sample dispensing channel 1051 between injection port 101 and capillary pump 103 to receive a first preset volume of sample microfluidic from injection channel 102. Reaction channel 1041 includes a photodeformable material such that the microfluidic is driven through reaction channel 1041 by a Laplace pressure difference generated by asymmetric photodeformation of reaction channel 1041. Reaction unit 110B includes a reaction channel 1042 arranged in a ring. Reaction channel 1042 is configured to communicate with injection channel 102 via sample dispensing channel 1052 between injection port 101 and capillary pump 103 to receive a second preset volume of sample microfluidic from injection channel 102. The reaction channel 1042 includes a photodeformable material that allows the microfluidic fluid to be driven through the reaction channel 1042 under the Laplace pressure difference generated by the asymmetric photodeformation of the reaction channel 1042.
[0026] Reaction unit 110A further includes a first connecting structure 1061, which is configured to communicate with reaction channel 1041 at one end and remain open to the atmosphere at the other end, so that the sample microfluidic can self-close the first connecting structure 1061 after entering the first connecting structure 1061 from the sample dispensing channel 1051 via the reaction channel 1041. Reaction unit 110B further includes a first connecting structure 1062, which is configured to communicate with reaction channel 1042 at one end and remain open to the atmosphere at the other end, so that the sample microfluidic can self-close the first connecting structure 1062 after entering the first connecting structure 1062 from the sample dispensing channel 1052 via the reaction channel 1042.
[0027] The first connection point CP11 between the sample distribution channel 1051 and the reaction channel 1041 and the second connection point CP21 between the reaction channel 1041 and the first connecting structure 1061 are spaced apart from each other along the longitudinal centerline of the reaction channel 1041. The first connection point CP12 between the sample distribution channel 1052 and the reaction channel 1042 and the second connection point CP22 between the reaction channel 1042 and the first connecting structure 1062 are spaced apart from each other along the longitudinal centerline of the reaction channel 1042.
[0028] In the microfluidic chip 100, the cross-sectional area of the sample inlet channel 102 is larger than that of the reaction channels 1041-1042. This facilitates the flow of microfluidic fluid from the sample inlet channel 102 into the reaction channels 1041-1042 under the influence of a Laplace pressure difference. The cross-sectional area of the reaction channels 1041-1042 is larger than that of the first connecting structures 1061-1062. This facilitates the flow of microfluidic fluid from the reaction channels 1041-1042 into the first connecting structures 1061-1062 under the influence of a Laplace pressure difference. The cross-sectional area of the reaction channels 1041-1042 is larger than that of the dispensing channels 1051-1052. The dispensing channels 1051-1052 can be used as liquid bridges between the reaction channels 1041-1042 and the sample inlet channel 102.
[0029] Therefore, after the sample microfluidic enters the injection channel 102 from the injection port 101, the sample microfluidic will proceed through the injection channel 102 under the action of the Laplace pressure difference generated by the capillary pump 103. When it reaches the connection point between each sample channel 1051-1052 and the injection channel 102, it will enter the corresponding reaction channel 1041-1042 through each sample channel 1051-1052 under the action of the Laplace pressure difference generated because the cross-sectional area of the injection channel 102 is greater than the cross-sectional area of the reaction channel 1041-1042.
[0030] When the sample microfluidic enters the sampling channel 1051 (1052) and reaches the first connection point CP11 (CP12) between the sampling channel 1051 (1052) and the reaction channel 1041 (1042), the sample microfluidic will flow from the first connection point CP11 (CP12) along the reaction channel 1041 (1042) to both sides (in) Figure 1In the middle, the flow is both clockwise and counterclockwise, while the gas originally inside the reaction channel 1041 (1042) can be discharged through the first connecting structure 1061 (1062). When the sample microfluidic reaches the second connection point CP21 (CP22) between the reaction channel 1041 (1042) and the first connecting structure 1061 (1062), it will enter the first connecting structure 1061 (1062) under the action of the Laplace pressure difference generated by the fact that the cross-sectional area of the reaction channel 1041 (1042) is larger than the cross-sectional area of the first connecting structure 1061 (1062). Once the sample microfluidic enters the first connecting structure 1061 (1062) with a very small cross-sectional area, it will form a liquid column that seals the first connecting structure 1061 (1062). When the first connecting structure 1061 (1062) is closed, the gas in the reaction channel 1041 (1042) can no longer be discharged from the first connecting structure 1061 (1062), and the sample microfluidic cannot overcome the gas pressure in the reaction channel 1041 (1042) to continue moving to both sides. Therefore, after the sample microfluidic enters the reaction channel 1041 (1042) from the first connection point CP11 (CP12), it can move as far as the minimum distance between the first connection point CP11 (CP12) and the second connection point CP21 (CP22) along the longitudinal centerline of the reaction channel 1041 (1042). (This minimum distance is the first distance between the first connection point and the second connection point along the longitudinal centerline of the reaction channel in the first direction (e.g., clockwise) and the distance between the first connection point and the second connection point along the longitudinal centerline of the reaction channel.) The sample microfluid that fails to enter the reaction channel 1041 (1042) and remains in the sample injection channel 102 will be drawn away by the capillary pump 103, leaving a section of sample microfluid between the second connection point CP21 (CP22) and the second connection point CP21 (CP22) at the symmetrical point CP21' (CP22') about the first connection point CP11 (CP12) on the longitudinal center line of the reaction channel 1041 (1042). It can be seen that such a measurement process is spontaneously achieved under the action of Laplace pressure difference, without the need for any external power pump valve assembly to drive it, and without requiring the sample microfluid to continuously fill the channels placed in front of the reaction units 110A-110B.
[0031] Through the above measurement process, reaction unit 110A can hold a section of sample microfluidic fluid between the second connection point CP21 and the symmetry point CP21' (passing through the first connection point CP11), while reaction unit 110B can hold a section of sample microfluidic fluid between the second connection point CP22 and the symmetry point CP22' (passing through the first connection point CP12). The sample dispensing channels 1051-1052 and the first connecting structures 1061-1062 can be the finest channels in the microfluidic chip 100, and their volumes can be configured to be negligible compared to the volume of reaction channel 1041 between CP21 and CP21' and the volume of reaction channel 1042 between CP22 and CP22'. Therefore, the first preset volume of the sample microfluidic measured by reaction unit 110A can be substantially equal to the volume of reaction channel 1041 between CP21 and CP21', which is determined based on twice the minimum distance between the first connection point CP11 and the second connection point CP21 along the longitudinal centerline of reaction channel 1041 and the cross-sectional area of reaction channel 1041; the second preset volume of the sample microfluidic measured by reaction unit 110B can be substantially equal to the volume of reaction channel 1042 between CP22 and CP22', which is determined based on twice the minimum distance between the first connection point CP21 and the second connection point CP22 along the longitudinal centerline of reaction channel 1042 and the cross-sectional area of reaction channel 1042. In some embodiments, reaction units 110A-110B are configured to receive the same preset volume of sample microfluidic from injection channel 102, for example, as shown in the figure. Figure 1 As shown (assuming in) Figure 1 (The cross-sectional areas of reaction channels 1041-1042 are the same). In other embodiments, reaction units 110A-110B are configured to receive sample microfluidics of different preset volumes from sample inlet channel 102, for example, Figure 3 As shown (assuming in) Figure 3 The cross-sectional areas of reaction channels 1041-1042 are the same.
[0032] Additionally, the depth of reaction channels 1041-1042 can be greater than the depth of sample dispensing channels 1051-1052. Due to the depth difference between sample dispensing channels 1051-1052 and reaction channels 1041-1042, a step can be formed at the first connection point CP11-CP12 between sample dispensing channels 1051-1052 and reaction channels 1041-1042. In some embodiments, the depth difference between sample dispensing channels 1051-1052 and reaction channels 1041-1042 can be configured to allow microfluidics to move within reaction channels 1041-1042 across the first connection point CP11-CP12 between sample dispensing channels 1051-1052 and reaction channels 1041-1042. Since the Laplace pressure difference generated by asymmetric photoinduced deformation can only effectively overcome flow resistance and drive fluid in a straight-through pipe with low flow resistance, a significant difference is required between the depths of the sampling channels 1051-1052 and the reaction channels 1041-1042. If the depths of the sampling channels 1051-1052 and the reaction channels 1041-1042 are close, then the pipe shape (close to a tee) at the first connection point CP11-CP12 of the reaction channels 1041-1042 is significantly different from the pipe shape (straight-through pipe) of the reaction channels 1041-1042 outside the first connection point. This will hinder the photoinduced drive of the microfluidics within the reaction channels 1041-1042, making it difficult to move freely from one end of the reaction channels 1041-1042 across the first connection point to the other end. Furthermore, in some examples, the ratio of the depth of the sampling channels 1051-1052 to the depth of the reaction channels 1041-1042 is less than 1:2. In some examples, the ratio of the depth of the sampling channels 1051-1052 to the depth of the reaction channels 1041-1042 is less than or equal to 1:4. When the ratio of the depth of the sampling channels 1051-1052 to the depth of the reaction channels 1041-1042 meets this requirement, the influence of the first connection point CP11-CP12 between the sampling channels 1051-1052 and the reaction channels 1041-1042 on the microfluidic photodynamic actuation within the reaction channels 1041-1042 can be reduced. Similarly, in some embodiments, the difference between the depth of the first connecting structures 1061-1062 and the depth of the reaction channels 1041-1042 can be configured to allow the microfluidic fluid to move within the reaction channels 1041-1042 across the second connection points CP21-CP22 between the first connecting structures 1061-1062 and the reaction channels 1041-1042. In some examples, the ratio of the depth of the first connecting structures 1061-1062 to the depth of the reaction channels 1041-1042 is less than 1:2.In some examples, the ratio of the depth of the first connecting structure 1061-1062 to the depth of the reaction channel 1041-1042 is less than or equal to 1:4. In some embodiments, the depth of the first connecting structure 1061-1062 may be equal to the depth of the sampling channel 1051-1052. In some embodiments, a transition channel providing a depth transition may be provided between the sampling channel 1051 (1052) and the reaction channel 1041 (1042) and / or between the first connecting structure 1061 (1062) and the reaction channel 1041 (1042).
[0033] The depth and width dimensions of each channel in the microfluidic chip 100 described in this article can be, for example, 10⁻¹⁰. 3 Within the micrometer range. In some embodiments, the width and depth of each of the sample introduction channel 102, the sample dispensing channels 1051-1052, the reaction channels 1041-1042, and the first connecting structure 1061-1062 are between 10 micrometers and 2000 micrometers, respectively, for example, between 50 micrometers and 1000 micrometers. Within this range, the fabrication difficulty of the microfluidic chip 100 is moderate, and the performance of the photo-driven fluid is also good. In a non-limiting example, the width and depth of the injection channel 102 can be 300 micrometers, the width and depth of the reaction channels 1041-1042 can be 200 micrometers, and the width and depth of the dispensing channels 1051-1052 and the first connecting structures 1061-1062 can be 200 micrometers and 50 micrometers, respectively. Based on these dimensions, it can be determined that the fluid volume within the dispensing channels 1051-1052 and the first connecting structures 1061-1062 has a negligible impact on measurement accuracy. In some examples, the volume of the reaction channel 1041 between CP21 and CP21' and the volume of the reaction channel 1042 between CP22 and CP22' can be between 50 nanoliters and 1000 nanoliters, or between 100 nanoliters and 700 nanoliters. Since the volume of reaction channel 1041 between CP21 and CP21' and the volume of reaction channel 1042 between CP22 and CP22' can be very small, the measurement of such a preset volume of microfluidic sample can be regarded as a simple and accurate quantitative measurement of trace samples. However, those skilled in the art will understand that the specific design of the volume of reaction channel 1041 between CP21 and CP21' and the volume of reaction channel 1042 between CP22 and CP22' can be determined according to the specific application scenario of the microfluidic chip 100.
[0034] It should be understood that the different cross-sectional areas of the channels designed above can be achieved by controlling the channel width to be the same while changing the channel depth, or by controlling the channel depth to be the same while changing the channel width, or by changing both the channel depth and width simultaneously. In some cases, controlling the channel width to be the same while changing the channel depth to achieve different cross-sectional areas may be preferred. For example, when forming channels using high-precision Computerized Numerical Control (CNC) machine tools, controlling the channel width to be the same while changing the channel depth may be more convenient to implement.
[0035] Reference Figure 1 and Figure 6 In some embodiments, the microfluidic chip 100 may include a substrate 10 having an inlet 101 and a groove communicating with the inlet 101 thereon, and a photodeformation film 20 attached to the substrate 10 (for clarity, in...). Figures 1 to 5 Only substrate 10 is shown in the image, and... Figures 1 to 5(The photodeformation film 20 is not shown in the diagram). The photodeformation film 20 at least partially covers the groove, thus forming a closed channel 30 together with the groove. This allows the microfluidic fluid to be driven through the closed channel 30 under the Laplace pressure difference generated by the asymmetric photodeformation of the closed channel 30. The closed channel 30 may provide at least reaction channels 1041-1042. In some embodiments, the closed channel 30 may also provide other channels of the microfluidic chip 100, such as sample inlet channels 102, sample dispensing channels 1051-1052, first connecting structures 1061-1062, etc. However, even if the upper surface of these other channels is formed by the photodeformation film 20, the fluid in them will not be photodriven when their upper surfaces do not undergo photodeformation. For example, grooves can be formed on the substrate 10 by CNC machining as the bottom and side surfaces of the closed channel 30, and after CNC machining is completed, the photodeformation film 20 is covered on the grooves as the upper surface of the closed channel 30 to obtain a complete channel structure. In some embodiments, to reduce the difficulty of CNC machining and improve measurement accuracy, the cross-sectional shape of the channel can be rectangular. However, this is merely exemplary and not limiting; the channel can also have other suitable cross-sectional shapes. In some examples, the substrate 10 can be an acrylic substrate, which not only meets the material requirements of microfluidic chips and CNC machining but also has good transparency, making it easier to observe the microfluidic state within the microfluidic chip. The photodeformable material can be any suitable photodeformable material known now or to be developed later. In some examples, the photodeformable material can include a photodeformable liquid crystal polymer, for example, a single film made of a photodeformable liquid crystal polymer can be used as the photodeformable film 20. In some examples, the photodeformable liquid crystal polymer can include a photoresponsive linear liquid crystal polymer with a polycyclooctene main chain and azobenzene side chains. In some embodiments, the substrate 10 and the photodeformable film 20 can be recyclable and reusable. For example, used but undamaged acrylic substrates can be recycled as brand-new components to produce new microfluidic chips after thorough cleaning and drying. Similarly, thin films made of photodeformable liquid crystal polymers can be prepared by dissolving and then extracting the original material to re-prepare thin films for the production of new microfluidic chips.
[0036] When specific illumination conditions are met, the photodeformable material (e.g., the photodeformable film 20) can undergo localized photodeformation, resulting in a change in the cross-sectional area of the local channels. Under the influence of the Laplace pressure difference, the fluid within the channels will move in the direction of decreasing cross-sectional area. In some embodiments, the photodeformable material (e.g., the photodeformable film 20) is configured to expand in response to illumination, such that portions of reaction channels 1041-1042 have a larger cross-sectional area when illuminated compared to when not illuminated, thereby driving the microfluidic fluid in reaction channels 1041-1042 in the direction of decreasing light intensity. In some embodiments, the photodeformable material (e.g., the photodeformable film 20) is configured to contract in response to illumination, such that portions of reaction channels 1041-1042 have a smaller cross-sectional area when illuminated compared to when not illuminated, thereby driving the microfluidic fluid in reaction channels 1041-1042 in the direction of increasing light intensity.
[0037] refer to Figure 6 The diagram illustrates the plane containing the length and depth, using the case of photosensitive expansion of the photodeformation film 20 as a non-limiting example: The microfluidic 40 is at position a (represented by the position of the left end face of the microfluidic 40), and the cross-sectional areas of each part of the closed channel 30 are initially the same. After irradiating the photodeformation film 20 at position a with light capable of causing expansion, the portion of the photodeformation film 20 at position a expands due to light, resulting in an increase in the cross-sectional area of the portion of the closed channel 30 at position a, which is larger than the cross-sectional area of the portion of the closed channel 30 at position b. This asymmetric photodeformation of the closed channel 30 at positions a and b generates a Laplace pressure difference, and under the influence of this Laplace pressure difference, the microfluidic 40 spontaneously moves from position a with a larger cross-sectional area to position b with a smaller cross-sectional area, thus achieving photo-driven microfluidic 40. Using this principle, the photo-driven microfluidic 40 can be precisely controlled by controlling the position and intensity of the light illumination. This photodynamic actuation method requires no external driving device; it can achieve contactless actuation of microfluidics using only a suitable light source. Furthermore, it offers high actuation precision.
[0038] In some embodiments, such as Figure 1 As shown, the first connecting structure 1061 (1062) includes an equilibrium channel 10611 (10621) that is connected at one end to the corresponding reaction channel 1041 (1042) and at the other end to the atmosphere. The cross-sectional area of the equilibrium channel 10611 (10621) is smaller than that of the reaction channel 1041 (1042). In some examples, the end of the equilibrium channel 10611 (10621) is formed to be open to the atmosphere, such as... Figure 1As shown. In some examples, the end of the balancing channel 10611 (10621) includes a balancing cavity 10612 (10622) having a vertical through-hole for communication with the atmosphere, such as Figure 2 As shown. Such a via can penetrate vertically through, for example, the substrate 10 and the photodeformation film 20. In some embodiments, the first connecting structure 1061 (1062) includes a balance channel 10611 (10621), or referred to herein as the trunk, which is connected at one end to the corresponding reaction channel 1041 (1042) and at the other end to the atmosphere, and branches 10613 (10623) with closed ends branching off from the trunk, as shown. Figure 3 As shown. Figure 3 The arrangement of the first interconnected structure shown facilitates more precise and stable measurement of the reaction unit. This is because when the sample microfluidic enters the main trunk and reaches its intersection with a branch, a portion of the sample microfluidic continues to move forward in the main trunk while another portion enters the branch. Since the end of the branch is closed, the sample microfluidic entering the branch compresses the gas within the branch, which makes the process more efficient than in the case of no branch (e.g., as shown in the diagram). Figure 1 As shown, the sample microfluidic fluid in the main trunk could not overcome the air pressure to continue moving forward earlier, so the first connecting structure 1061 (1062) self-closed earlier.
[0039] In some embodiments, the first connecting structure may be arranged outside the reaction channel. For example, see reference... Figure 1 and Figure 2 A first connecting structure 1061 is disposed outside the reaction channel 1041, and a first connecting structure 1062 is disposed outside the reaction channel 1042. In some embodiments, the first connecting structure may be disposed inside the reaction channel. For example, refer to... Figure 3 The first connecting structure 1061 is arranged inside the reaction channel 1041.
[0040] In some embodiments, such as reference Figures 2 to 4The microfluidic chip 100 may further include a buffer tube 107 connected between the sample inlet channel 102 and the capillary pump 103. In some embodiments, the cross-sectional area of the buffer tube 107 is larger than the cross-sectional area of the sample inlet channel 102. In some embodiments, the buffer tube 107 may include one or more connected U-shaped tubes. The arrangement of the buffer tube 107 can help prevent the sample microfluidic fluid from being drawn away by the capillary pump before the first connecting structure 1061-1062 self-closes. In other words, the arrangement of the buffer tube 107 can help ensure that the sample microfluidic fluid is drawn away by the capillary pump only after the first connecting structure 1061-1062 self-closes (i.e., the reaction units 110A-110B have completed the measurement process). The arrangement of the buffer tube 107 can also prevent the sample microfluidic fluid from flowing back from the capillary pump 103 to the sample inlet channel 102. Alternatively, instead of providing a buffer tube 107, the end portion of the sample inlet channel 102 near the capillary pump 103 can be formed into multiple interconnected bends and / or the bottom surface of the end portion of the sample inlet channel 102 near the capillary pump 103 can be formed into multiple steps, which can also provide a buffer area for the sample microfluidic.
[0041] In some embodiments, the sample inlet channel 102 can be configured as a U-shaped channel, and the sample dispensing channels 1051-1052 can be connected downstream of the bend section of the U-shaped channel. This helps to maintain the flow rate and flow volume of the sample microfluidic inlet 101 within the sample inlet channel 102 within a controllable range. The bend section of the U-shaped channel can also effectively achieve the effects of buffering and liquid storage, and also reduces the footprint of the sample inlet channel 102 in the microfluidic chip 100, making the arrangement of the sample inlet channel 102 more reasonable.
[0042] In some embodiments, when the microfluidic chip 100 includes multiple reaction units, these reaction units may be located on the same side of the injection channel 102 or on different sides of the injection channel 102. When two reaction units are located on different sides of the injection channel 102, the dispensing channels of the two reaction units may be aligned with each other or offset from each other.
[0043] In some embodiments, pre-prepared reactants are stored at one or more different locations in reaction channels 1041-1042, and the sample microfluidic can be driven to each of the one or more different locations under the Laplace pressure difference generated by the asymmetric photodeformation of reaction channels 1041-1042 to contact, mix, and / or react with the pre-prepared reactants at that location. In some examples, these pre-prepared reactants may be added to reaction channels 1041-1042 in advance during the manufacturing stage of microfluidic chip 100. For example, after grooves are formed in substrate 10, reactants can be pre-placed at specific locations in the grooves of substrate 10 to be used as reaction channels by freeze-drying, then a photodeformation film 20 can be covered on substrate 10, and then the substrate 10 covered with the photodeformation film 20 can be encapsulated to obtain microfluidic chip 100.
[0044] The sample microfluid and / or its mixture with pre-prepared reactants and / or reaction products can be detected directly at the reaction channel, such as through fluorescence detection, absorbance detection, etc. Alternatively, a detection channel can be additionally configured to connect to the reaction channel and receive the microfluid to be detected from it. In some embodiments, each reaction unit in some or all of the reaction units of the microfluidic chip 100 may further include: a second communication structure configured to communicate with a reaction channel at one end and with the atmosphere at the other end; a detection channel configured to communicate with the reaction channel at one end to receive microfluidic material to be detected from the reaction channel, and to communicate with the atmosphere at the other end via a third communication structure, wherein a first distance between the reaction channel and the third connection point of the second communication structure and the first connection point in a first direction (e.g., clockwise) along the longitudinal centerline of the reaction channel is greater than a minimum distance between the first connection point and the second connection point along the longitudinal centerline of the reaction channel, and a second distance between the third connection point and the first connection point in a second direction opposite to the first direction (e.g., counterclockwise) along the longitudinal centerline of the reaction channel is greater than a minimum distance between the first connection point and the second connection point along the longitudinal centerline of the reaction channel, wherein the communication between each of the second and third communication structures and the atmosphere is switchable, and wherein the cross-sectional area of the reaction channel is greater than the cross-sectional area of the detection channel.
[0045] For example, refer to Figure 4The reaction unit 110A includes a second communication structure 1081 that communicates with the reaction channel 1041 at one end and with the atmosphere at the other end. The communication between the second communication structure 1081 and the atmosphere is switchable. A first distance (e.g., clockwise) along the longitudinal centerline of the reaction channel 1041 between the third connection point CP31 and the first connection point CP11 of the reaction channel 1041 is greater than the minimum distance (e.g., along the longitudinal centerline of the reaction channel 1041) between the first connection point CP11 and the second connection point CP21. A second distance (e.g., counterclockwise) along the longitudinal centerline of the reaction channel 1041 between the third connection point CP31 and the first connection point CP11 is greater than the minimum distance (e.g., along the longitudinal centerline of the reaction channel 1041) between the first connection point CP11 and the second connection point CP21. In other words, since the sample microfluidic can move as far as the minimum distance between the first connection point CP11 and the second connection point CP21 along the longitudinal center line of the reaction channel 1041 after entering the reaction channel 1041 from the first connection point CP11, the sample microfluidic will not reach the second connecting structure 1081 in the reaction channel 1041 when the reaction unit 110A completes the measurement process.
[0046] Additionally, reaction unit 110B includes a second communication structure 1082 that communicates with reaction channel 1042 at one end and with the atmosphere at the other end. The communication between the second communication structure 1082 and the atmosphere is switchable. A first distance (e.g., clockwise) along the longitudinal centerline of reaction channel 1042 between the third connection point CP32 of reaction channel 1042 and the first connection point CP12 is greater than the minimum distance along the longitudinal centerline of reaction channel 1042 between the first connection point CP12 and the second connection point CP22. A second distance (e.g., counterclockwise) along the longitudinal centerline of reaction channel 1042 between the third connection point CP32 and the first connection point CP12 is greater than the minimum distance along the longitudinal centerline of reaction channel 1042 between the first connection point CP12 and the second connection point CP22. In other words, since the sample microfluidic can move as far as the minimum distance between the first connection point CP12 and the second connection point CP22 along the longitudinal center line of the reaction channel 1042 after entering the reaction channel 1042 from the first connection point CP12, the sample microfluidic will not reach the second connecting structure 1082 in the reaction channel 1042 when the reaction unit 110B completes the measurement process.
[0047] Continue to refer to Figure 4The reaction unit 110A further includes a detection channel 1121, configured to communicate with the reaction channel 1041 at one end to receive the microfluidic to be detected from the reaction channel 1041, and to communicate with the atmosphere at the other end via a third communication structure 1131, the communication of the third communication structure 1131 with the atmosphere being switchable. The cross-sectional area of the reaction channel 1041 is larger than the cross-sectional area of the detection channel 1121. Additionally, the reaction unit 110B includes detection channels 1122-1123, each configured to communicate with the reaction channel 1042 at one end to receive the microfluidic to be detected from the reaction channel 1042, and to communicate with the atmosphere at the other end via corresponding third communication structures 1132-1133, the communication of the third communication structures 1132-1133 with the atmosphere being switchable. The cross-sectional area of the reaction channel 1042 is larger than the cross-sectional area of the detection channels 1122-1123.
[0048] When detection is not required (e.g., before the reaction is complete), the connections between the second connecting structure 1081 (1082) and the third connecting structure 1131 (1132-1133) and the atmosphere can be closed. At this time, the gas in the detection channel 1121 (1122-1123) prevents the microfluidic fluid in the reaction channel 1041 (1042) from entering the detection channel 1121 (1122-1123). When detection is required, the connection between the third connecting structure 1131 (1132-1133) and the atmosphere can be opened. At this time, the microfluidic fluid in the reaction channel 1041 (1042) spontaneously enters the detection channel 1121 (1122-1123) under the Laplace pressure difference generated because the cross-sectional area of the reaction channel 1041 (1042) is greater than that of the detection channel 1121 (1122-1123). However, in some cases, the microfluidic fluid entering detection channels 1121 (1122-1123) may seal them off, preventing the microfluidic fluid still remaining in reaction channel 1041 (1042) from entering further. For example, when reaction channel 1041 (1042) is not connected to the atmosphere, opening the third connection structure 1131 (1132-1133) to the atmosphere will create a negative pressure within reaction channel 1041 (1042), thus hindering the microfluidic fluid in reaction channel 1041 (1042) from entering detection channel 1121 (1122-1123). In such cases, the amount of microfluidic fluid already in detection channel 1121 (1122-1123) may be sufficient for detection. However, the amount of microfluidic material that has entered detection channel 1121 (1122-1123) may not be sufficient for detection. For example, some detections may require all the microfluidic material in reaction channel 1041 (1042) to enter detection channel 1121 (1122-1123). Therefore, the second connecting structure 1081 (1082) and the third connecting structure 1131 (1132-1133) can be simultaneously connected to the atmosphere. This prevents the formation of negative pressure in reaction channel 1041 (1042), allowing the microfluidic material in reaction channel 1041 (1042) to smoothly enter detection channel 1121 (1122-1123).
[0049] The detection channels 1121-1123 can have any suitable geometry, as long as the cross-sectional area of the detection channels 1121-1123 is smaller than the cross-sectional area of the reaction channels 1041-1042. In some embodiments, the detection channels 1121-1123 can be arranged in a spiral shape. Compared to a linear arrangement, a spiral arrangement of detection channels can increase the distribution density of the microfluidic fluid to be detected on the microfluidic chip 100, which facilitates improved detection accuracy and efficiency, and can also accommodate more microfluidic fluid to be detected. Although Figure 4The outline of each turn of the spiral of detection channels 1121-1123 is shown as basically square, but it can also have other suitable outline shapes. For example, the outline of each turn of the spiral of detection channels 1121-1123 can also be basically triangular, quadrilateral, pentagonal, or other polygonal, circular, elliptical, etc., without limitation.
[0050] The detection channel can be positioned either outside or inside the reaction channel. For example, as... Figure 4 As shown, detection channel 1121 is arranged outside reaction channel 1041, while detection channels 1122-1123 are arranged inside reaction channel 1041. Each reaction channel may be connected to one or more detection channels to perform one or more identical or different detections. In some embodiments, each reaction unit may include at least two detection channels spaced apart from each other, such as... Figure 4 As shown, the reaction unit 110B includes detection channels 1122 and 1123 spaced apart from each other. These detection channels may be located on the same side or different sides of the reaction channel. When multiple detection channels are located on the same side of the reaction channel, the connection portions of these detection channels and the reaction channel may be shared or separate. When multiple detection channels are located on different sides of the reaction channel, the connection portions of these detection channels and the reaction channel may be aligned or offset from each other. In some embodiments, a fourth connection point between the detection channel and the reaction channel may be separated from the first connection point between the sample dispensing channel and the reaction channel, for example, as shown in the figure. Figure 4 As shown, the fourth connection point CP41 (CP42) is separated from the first connection point CP11 (CP12). In some embodiments, the fourth connection point may coincide with the first connection point, for example, as shown in the figure. Figure 5 As shown, the fourth connection point CP4A (CP4B) coincides with the first connection point CP1A (CP1B).
[0051] In some embodiments, detection channels 1121-1123 may have a different depth than reaction channels 1041-1042. In such embodiments, a transition channel providing a depth transition may be provided between detection channels 1121-1123 and reaction channels 1041-1042. In some embodiments, the depth of detection channels 1121-1123 may be less than the depth of reaction channels 1041-1042.
[0052] The communication between the second communication structures 1081-1082 and the third communication structures 1131-1133 and the atmosphere can be controlled by any suitable switching mechanism. In some examples, a movable baffle or other closing structure can be provided at the opening of the communication structure that can be opened to the atmosphere (e.g., a through-hole of a balancing cavity), the baffle being movable between a first position closing the opening and a second position not closing the opening. In some examples, baffles for multiple communication structures can be integrated onto the same baffle card, thereby enabling the switching of different communication structures or combinations thereof by moving the baffle card as a whole. In some embodiments, the communication between the communication structure and the atmosphere can be controlled by a photoresponsive switching mechanism. Such a photoresponsive switching mechanism may include a photodeformable material. In some examples, the photodeformable material may not close the opening of the communication structure when not exposed to light, but may undergo photodeformation (e.g., expansion) to close the opening of the communication structure when exposed to light. In other examples, the photodeformable material may close the opening of the communication structure when not exposed to light, but may undergo photodeformation (e.g., contraction) to not close the opening of the communication structure when exposed to light. For example, a chamber containing photodeformable gel can be provided at the opening of the connected structure, or a thin film or plate formed of photodeformable material can be provided at the opening of the connected structure.
[0053] In some embodiments, the microfluidic chip may further include multiple independent microfluidic units. As a non-limiting example, refer to... Figure 5 The microfluidic chip 100 includes two independent microfluidic units 100UA and 100UB. Each of the microfluidic units 100UA and 100UB is not limited to... Figure 5 The exemplary arrangement shown is not applicable; rather, it can have an arrangement of microfluidic units according to any embodiment of this disclosure. Figure 5 As shown, the microfluidic unit 100UA includes an inlet 101A, an injection channel 102A, a capillary pump 103A, and a reaction channel 104A. The reaction channel 104A is connected to the dispensing channel 105A at a first connection point CP1A, and then communicates with the injection channel 102A. The reaction channel 104A is connected to a first communication structure 106A at a second connection point CP2A and to a second communication structure 108A at a third connection point CP3A. The reaction channel 104A is also connected to two spaced-apart detection channels 112A at a fourth connection point CP4A. These two detection channels 112A provide two spaced-apart detection regions. Further as... Figure 5As shown, the microfluidic unit 100UB includes an inlet 101B, an injection channel 102B, a capillary pump 103B, and a reaction channel 104B. The reaction channel 104B is connected to the dispensing channel 105B at a first connection point CP1B, and then communicates with the injection channel 102B. The reaction channel 104B is connected to a first communication structure 106B at a second connection point CP2B and to a second communication structure 108B at a third connection point CP3B. The reaction channel 104B is also connected to two spaced-apart detection channels 112B at a fourth connection point CP4B. These two detection channels 112B provide two spaced-apart detection regions. Because the microfluidic units 100UA and 100UB are independent of each other, they can be used separately for the detection of microfluidics in different samples.
[0054] The microfluidic chip 100 provided in this disclosure can be used for at least one of the following: immunoassay, biochemical assay, molecular assay, and polymerase chain reaction (PCR) assay. Figure 4Taking the microfluidic chip 100 as an example, reaction units 110A and 110B can correspond to any two of the three dry biochemical assays: serum creatinine, serum urea, and serum uric acid. The samples required for these dry biochemical assays are all serum. It is understood that the microfluidic unit 100U of the microfluidic chip 100, in addition to reaction units 110A and 110B, can also include a third reaction unit, so that the three reaction channels can correspond to the three dry biochemical assays: serum creatinine, serum urea, and serum uric acid, respectively. Taking the serum creatinine dry biochemical assay using reaction unit 110A as an example, serum, as a sample microfluidic, is added to the inlet 101 and enters the injection channel 102, then enters the reaction channel 1041 via the dispensing channel 1051. The serum is first mixed with a first detection reagent pre-embedded at the inlet (i.e., the first connection point CP11) of the reaction channel 1041 by lyophilization. No reaction occurs during mixing, and the mixture is then incubated at 37°C for 5 minutes. After incubation, the mixture of serum and the first detection reagent is driven to another location in reaction channel 1041 via photo-driven microfluidics to mix with and react with the second detection reagent pre-embedded in that location via lyophilization. The mixture is then incubated at 37°C for 5 minutes. After incubation, the reaction product of the serum-first detection reagent mixture and the second detection reagent is driven to the fourth connection point CP41 between detection channel 1121 and reaction channel 1041 via photo-driven microfluidics. Then, the second connecting structure 1081 and the third connecting structure 1131 are opened to the atmosphere, allowing the reaction product to enter detection channel 1121. The absorbance of the reaction product in the detection area provided by detection channel 1121 is measured. Specifically, the absorbance of the reaction product to light at a wavelength of 550 nm can be measured at a certain moment and again two minutes later. The difference between the two detected absorbance values is calculated and recorded as the result of this dry biochemical assay for serum creatinine. Like reaction unit 110B, which has multiple detection channels to provide multiple detection areas, different detections can be performed on different detection areas. For example, absorbance detection can be performed on the detection area provided by detection channel 1122, while fluorescence detection can be performed on the detection area provided by detection channel 1123. This can be configured according to specific detection needs. Additionally, like... Figure 5 The microfluidic chip 100 has multiple microfluidic units, each with a separate sample inlet, which can be used for situations where the types of samples used in multiple detection projects are not exactly the same, or where the types of samples are the same but come from different subjects.
[0055] Furthermore, the same microfluidic chip can be used not only for detections using the same methodology (e.g., the aforementioned dry biochemical tests for serum creatinine, serum urea, and serum uric acid all belong to the same methodology, i.e., biochemical detection), but also for detections using different methodologies (e.g., immunoassay, biochemical detection, molecular detection, PCR detection, etc.). For example, when the microfluidic chip includes three reaction units, the first reaction unit can be used for dry biochemical detection of serum creatinine, the second reaction unit can be used for C-reactive protein (CRP) immunoturbidimetric detection, and the third reaction unit can be used for thyroid function immunofluorescence detection (homogeneous immunoluminescence detection). The detection process for CRP immunoturbidimetric detection is similar to that of dry biochemical detection of serum creatinine, involving mixing the sample with two test reagents sequentially and ultimately performing absorbance measurement. However, the wavelength used for absorbance measurement in CRP immunoturbidimetric detection differs from that used in dry biochemical detection of serum creatinine. In addition, the detection process of thyroid function immunofluorescence assay is similar to that of CRP immunoturbidimetric assay. However, thyroid function immunofluorescence assay does not perform absorbance detection but fluorescence detection. The intensity of the light emitted by the reaction product after being excited by light of a specific wavelength (i.e., fluorescence) is detected. The detected fluorescence intensity is recorded together with the results of the immunoluminescence assay.
[0056] The microfluidic chip disclosed herein is also particularly suitable for PCR detection. For endpoint PCR detection, the detection process is similar to that of the other methodologies mentioned above; simply allow the final reaction product to enter the detection channel after the PCR reaction is complete for detection. For real-time quantitative PCR detection, if a temperature-dependent PCR reaction is performed, multiple different temperature zones need to be formed at multiple non-adjacent locations in the reaction channel using temperature control components such as electric heaters. For example, a high-temperature zone and a low-temperature zone can be formed at two non-adjacent locations (or a high-temperature zone, a medium-temperature zone, and a low-temperature zone can be formed at three non-adjacent locations). Then, the mixture of sample microfluidic and detection reagent is oscillated and cycled between the high-temperature and low-temperature zones in the reaction channel by photo-driven microfluidics to achieve the denaturation-annealing-extension process. As the mixture moves from the low-temperature zone to the high-temperature zone, fluorescence detection can be performed on the mixture in the reaction channel, and the fluorescence intensity can be recorded. Plotting the fluorescence intensity measured for each cycle into a curve yields the results of real-time quantitative PCR detection. If an isothermal PCR reaction is performed, the microfluidic chip can be maintained at the desired temperature using temperature control components, and the other processes are similar to those described above.
[0057] In another aspect, this disclosure also provides a method for operating the aforementioned microfluidic chip.
[0058] refer to Figure 7Method 200 may include: at step S202, adding sample microfluidic fluid to the injection port to allow the added sample microfluidic fluid to enter the injection channel; at step S204, after the sample microfluidic fluid self-closes the first connecting structure of each reaction unit and is still retained in the injection channel and separates from the sample microfluidic fluid in each dispensing channel, selectively irradiating the reaction channel locally to allow the sample microfluidic fluid in the reaction channel to move in the reaction channel.
[0059] When the microfluidic chip also includes a detection channel (e.g., as shown in the example) Figure 4 and Figure 5 When referring to the microfluidic chip shown, refer to Figure 8 Method 200' includes: at step S202', disconnecting each of the second and third connecting structures from the atmosphere; at step S204', adding sample microfluidic fluid to the injection port to allow the added sample microfluidic fluid to enter the injection channel; at step S206', after the sample microfluidic fluid self-closes the first connecting structure of each reaction unit and remains in the injection channel, separating it from the sample microfluidic fluid in each dispensing channel, selectively illuminating a portion of the reaction channel to allow the sample microfluidic fluid in the reaction channel to move within the reaction channel; at step S208', after the reaction in the reaction channel has ended, selectively illuminating a portion of the reaction channel to drive the sample microfluidic fluid in the reaction channel to the fourth connection point between the detection channel and the reaction channel; and at step S210', connecting each of the second and third connecting structures to the atmosphere, thereby allowing the sample microfluidic fluid in the reaction channel to enter the detection channel. Other embodiments of the method can be found in those described above regarding the microfluidic chip 100, and will not be repeated here.
[0060] In another aspect, this disclosure also provides a microfluidic device including the aforementioned microfluidic chip.
[0061] refer to Figure 9A microfluidic device 300 is provided, comprising a microfluidic chip 100 according to any of the foregoing embodiments and a light source 310 configured to provide illumination to the microfluidic chip 100 to control the movement of microfluidics within the microfluidic chip 100 (especially in the reaction channel). The light source 310 can take any suitable form, such as a point light source, line light source, area light source, array light source, etc., and can be any suitable light source such as a light-emitting diode (LED) or laser. In some embodiments, the light source 310 can be configured to move relative to the microfluidic chip 100 to scan the illumination position on the microfluidic chip 100 to generate asymmetric photoinduced deformation along the channel (especially the reaction channel) and thereby drive the fluid. For example, the relative movement of the light source 310 and the microfluidic chip 100 can be achieved by fixing the light source 310 while moving the microfluidic chip 100, or by fixing the microfluidic chip 100 while moving the light source 310, or by allowing the light source 310 and the microfluidic chip 100 to move simultaneously at different speeds; no particular limitation is made here. In some embodiments, such as Figure 10 As shown, the light source 310 may include an array of multiple light sources 310_1, 310_2, and 310_3, each of which has a different illumination position on the microfluidic chip 100 (especially on the reaction channel). Therefore, the illumination position can be switched by turning each light source on and off. Although Figure 10 Only three light sources 310_1, 310_2, and 310_3 are shown in the figure, but this is merely exemplary and not restrictive. More light sources can be arranged as needed, and they can be arranged in any suitable array, such as a one-dimensional array or a two-dimensional array.
[0062] exist Figure 9 In this embodiment, it can be understood as providing a scanning of a positive-phase light spot on the microfluidic chip 100. In some other embodiments, a scanning of an inverted light spot on the microfluidic chip 100 may also be provided. For example, refer to... Figure 11The microfluidic device 300 may further include a light-shielding plate 320 disposed between the microfluidic chip 100 and the light source 310 and configured such that selectable portions of the reaction channels of the microfluidic chip 100 are not illuminated by the light source 310, while the remaining portions are illuminated by the light source 310. The light source 310 may, for example, be configured to provide illumination to the entire microfluidic chip 100, and the projection of the light-shielding plate 320 onto the microfluidic chip 100 provides an inverted light spot. The microfluidic chip 100 and the light source 310 may be fixed, while the light-shielding plate 320 may be movable, allowing selection of different selectable portions of the reaction channels of the microfluidic chip 100, effectively providing a scan of the inverted light spot. In other embodiments, the light-shielding plate 320 may also be configured such that selectable portions of the reaction channels of the microfluidic chip 100 are illuminated by the light source 310, while the remaining portions are not. For example, the light source 310 can be configured to provide illumination to the entire microfluidic chip 100, and the light shield 320 can block all the illumination except for the openings therein for light leakage. In this case, the microfluidic chip 100 and the light source 310 can be fixed, and the light shield 320 can be movable, so that different selectable portions of the reaction channels of the microfluidic chip 100 can be selected, which is equivalent to providing scanning of the positive phase light spot.
[0063] In other embodiments, reference is made to Figure 12 The microfluidic device 300 may alternatively include an optical attenuator 330 disposed between the microfluidic chip 100 and the light source 310 and configured to attenuate the intensity of the illumination from the light source 310 received by a selectable portion of the reaction channel of the microfluidic chip 100 compared to the illumination received by the remaining portion of the reaction channel. The light source 310 may, for example, be configured to provide illumination to the entire microfluidic chip 100, while the projection of the optical attenuator 330 onto the microfluidic chip 100 provides an attenuated light spot. The microfluidic chip 100 and the light source 310 may be fixed, while the optical attenuator 330 may be movable, allowing selection of different selectable portions of the reaction channel of the microfluidic chip 100, effectively providing a scan of the attenuated light spot.
[0064] It is understood that although the above description shows that the light-shielding plate 320 or the light-attenuating plate 320 moves while the light source 310 and the microfluidic chip 100 remain stationary, this is merely exemplary and not restrictive. The relative movement between the above components can be achieved in various ways, as long as it is possible to scan the positive phase spot, the negative phase spot, or the attenuated spot on the microfluidic chip 100.
[0065] To provide a higher degree of automation for the microfluidic device 300, in some embodiments, reference is made to... Figure 13The microfluidic device 300 may further include a controller 340. The controller 340 may be configured to perform the operating method of the microfluidic chip according to any of the foregoing embodiments. For example, the controller 340 may be configured to, after the sample microfluidic fluid in the first connected structure of each reaction unit of the self-sealing microfluidic chip and still remaining in the injection channel is separated from the sample microfluidic fluid in each dispensing channel, control a light source to selectively illuminate the reaction channel, causing the sample microfluidic fluid in the reaction channel to move within the reaction channel. In some embodiments, when each reaction unit of the microfluidic chip 100 further includes a detection channel (e.g., as shown in the figure), Figure 4 and Figure 5 When the microfluidic chip shown is used, the controller 340 can be configured to: before adding sample microfluidic fluid to the injection port, execute control to prevent each of the second and third connecting structures from communicating with the atmosphere; after the sample microfluidic fluid self-closes the first connecting structure of each reaction unit and the sample microfluidic fluid still remaining in the injection channel separates from the sample microfluidic fluid in each dispensing channel, control the light source to selectively illuminate the reaction channel, causing the sample microfluidic fluid in the reaction channel to move in the reaction channel; after the reaction in the reaction channel is completed, control the light source to selectively illuminate the reaction channel, driving the sample microfluidic fluid in the reaction channel to the fourth connection point of the detection channel and the reaction channel; execute control to connect each of the second and third connecting structures with the atmosphere, thereby allowing the sample microfluidic fluid in the reaction channel to enter the detection channel. Other operational embodiments of the controller 340 can be referred to those described above regarding the microfluidic chip 100, and will not be repeated here.
[0066] The microfluidic chip and microfluidic device disclosed herein effectively utilize the capillary force of the capillary pump and the Laplace pressure difference generated by the asymmetric photoinduced deformation of the channel to achieve contactless and precise microfluidic actuation without any external driving device. Furthermore, it can achieve precise quantitative trace measurement operations at the back end without filling the entire front channel. It has low sample loss, few components, small overall size, simple and robust structure, high repeatability, and a high degree of portability and automation.
[0067] In another aspect, this disclosure provides a microfluidic device that enables contactless actuation of microfluidics within a microfluidic chip using photodynamic microfluidic actuation, and is also applicable to detection and analysis using various methodologies. The microfluidic devices according to various embodiments of this disclosure are described below with reference to the accompanying drawings. It should be understood that actual microfluidic devices may include other components, but to avoid obscuring the essential points of this disclosure, these other components will not be discussed herein and are not shown in the drawings.
[0068] refer to Figure 14This illustration shows a microfluidic device 400 according to some embodiments of the present disclosure. The microfluidic device 400 includes a light control module 410 and a movement module 420, wherein the light control module 410 is fixed above the movement module 420. The light control module 410 includes a light source 411 configured to provide illumination to a microfluidic chip 460 to control the movement of microfluidics within the microfluidic chip 460. The microfluidics in the microfluidic chip 460 are photoactuable and may be, for example, but not limited to, the microfluidic chip 100 described in any embodiment of the present disclosure. (See reference...) Figure 16 The light emitted by light source 411 can be totally reflected onto microfluidic chip 460 by right-angle prism 412. The optical path design shown here is merely exemplary and not limiting; the optical path from light source 411 to microfluidic chip 460 can be designed with more, fewer, or alternative optical elements. The light control module 410 can be similarly referenced to the various configurations mentioned above regarding microfluidic device 300. Light source 411 can be any suitable light source such as an LED or laser. For example, light source 411 can include multiple LEDs of different wavelengths, which can form a group of light sources capable of switching wavelengths. Light source 411 can take any suitable form such as a point light source, line light source, area light source, array light source, etc., and components for changing the illumination pattern can be provided in the optical path from light source 411 to microfluidic chip 460. For example, in Figure 16 In the process, when the light source 411 originally provides a point light source on the microfluidic chip 460, a detachable light guide strip can be added below the right-angle prism 412 to convert the point light source into a line light source so as to perform batch photo-driven operation on multiple microfluidic chips.
[0069] Reference Figure 14 and Figure 16 The moving module 420 is configured to move the microfluidic chip 460 to adjust the relative position of the microfluidic chip 460 and the light source 411, so that the microfluidic chip 460 is selectively and locally illuminated by the light source 411, thereby photo-driven the microfluidics within the microfluidic chip 460. For example, as... Figure 15 As shown, in some embodiments, the moving module 420 may include a platform 421 and a motor assembly for driving the platform 421 to move in a horizontal plane. The upper surface of the platform 421 provides a bearing surface 4211 for placing the microfluidic chip 460. It should be understood that, although Figure 14Only one microfluidic chip is shown placed on the support surface 4211, but in some embodiments, multiple microfluidic chips may be placed on the support surface 4211. The motor assembly may include a first motor, or X-axis motor 4221, for driving the support platform 421 to move laterally in the horizontal plane (also referred to herein as the X-axis direction), and a second motor, or Y-axis motor 4231, for driving the support platform 421 to move longitudinally in the horizontal plane (also referred to herein as the Y-axis direction). The moving module 420 may also include a first guide portion, or X-axis guide portion 4222, for guiding the support platform 421 to move laterally in the horizontal plane, and a second guide portion, or Y-axis guide portion 4232, for guiding the support platform 421 to move longitudinally in the horizontal plane. The X-axis guide portion 4222 corresponds to the X-axis motor 4221, and the Y-axis guide portion 4232 corresponds to the Y-axis motor 4231. In some examples, each guide may include at least a set of lead screw and nut mechanisms and guide rails parallel to the guide direction. The nut in the lead screw and nut mechanism can be directly fixed to the bottom of the support platform 421, while the lead screw is arranged along the corresponding guide direction and connected to the output end of the corresponding motor. For example, when the X-axis motor 4221 outputs torque, due to the transmission action of the lead screw and nut mechanism, the support platform 421 can reciprocate along the X-axis direction, and under the guidance of the X-axis guide 4222, the support platform 421 can move more stably along the X-axis direction. In addition, the X-axis motor 4221 and the X-axis guide 4222 work independently of each other and do not interfere with each other. Therefore, the support platform 421 can move simultaneously in both the X-axis and Y-axis directions, thereby achieving the synthesis of movement in both directions, such as oblique or curved movement in a horizontal plane. In addition, to improve control accuracy and stability, servo motors can be selected as the X-axis motor 4221 and the Y-axis motor 4231. Guide rails 4241 and 4242 can also be arranged on the corresponding sides of the support platform 421 to prevent unilateral lateral displacement of the support platform 421. The support surface 4211 of the support platform 421 can also be provided with a device (e.g., a clamp) for fixing the microfluidic chip 460 to prevent the microfluidic chip 460 from deviating from the desired position due to slippage during the movement of the support platform 421.
[0070] Continue to refer to Figure 14In some embodiments, the microfluidic device 400 may further include a detection module 430 configured to perform detection on the microfluidic chip 460, wherein the detection module 430 is fixed above the moving module 420 and spaced apart from the light control module 410. The moving module 420 is also configured to move the microfluidic chip 460 to adjust the relative position of the microfluidic chip 460 and the detection module 430, so that the microfluidic chip 460 is detected by the detection module 430. For example, in the aforementioned biochemical detection, immunoassay, and other examples, the moving module 420 can be used to move the corresponding detection area of the microfluidic chip 460 into the detection field of view of the detection module 430. By staggering the detection module 430 and the light control module 410, and by moving the microfluidic chip 460 through the moving module 420, the relative movement between the microfluidic chip 460 and the light control module 410, as well as the relative movement between the microfluidic chip 460 and the detection module 430, is achieved. This reduces the number of moving parts in the microfluidic device 400, simplifies the structure of the microfluidic device 400, and reduces manufacturing difficulty and cost.
[0071] In some embodiments, the detection module 430 includes a plurality of detection units, the relative arrangement of which corresponds to the relative arrangement of a plurality of detection regions of the microfluidic chip 460. In some examples, the detection module 430 may include a fluorescence detection unit 431 and an absorbance detection unit 432, the distance between the fluorescence detection unit 431 and the absorbance detection unit 432 being configured to be the same as the distance between two detection regions of the microfluidic chip 460. For example, if the microfluidic chip 460 is... Figure 4 Taking the microfluidic chip 100 as an example, the distance between the fluorescence detection unit 431 and the absorbance detection unit 432 of the detection module 430 can be configured to be the same as the distance between the detection areas provided by the detection channels 1122 and 1123. Furthermore, especially in real-time quantitative PCR detection, to facilitate accurate capture of the position of the liquid to be detected by the fluorescence detection unit 431 during detection, the detection point of the fluorescence detection unit 431 can be configured to coincide with the light spot of the light source 411 of the light control module 410, without affecting the reciprocating oscillation cycle of the liquid to be detected. Here, the wavelength of the light source 411 used for photodynamic microfluidic driving can be different from the fluorescence wavelength detected by the fluorescence detection unit 431; therefore, simply setting a corresponding filter in the fluorescence detection unit 431 can eliminate the influence of other wavelengths of light on the detection results.
[0072] Continue to refer to Figure 14In some embodiments, the microfluidic device 400 may further include a temperature control module 440 (not explicitly shown) configured to control the temperature of the microfluidic chip 460, wherein the temperature control module 440 is arranged in the moving module 420, particularly in the support surface 4211. In some embodiments, the temperature control module 440 may include an electric heater and a temperature sensor. The electric heater may be arranged within the support surface 4211 to transfer heat to the microfluidic chip 460 by thermal conduction. Of course, other heat transfer methods and other heating forms are also feasible. In addition, a cooler or the like may be provided as needed. Since the microfluidic chip 460 is fixed on the support surface 4211 and there is no relative displacement between them, the electric heater can be arranged in the support surface 4211 at a position corresponding to the reaction unit of the microfluidic chip 460, thereby ensuring that the temperature is controllable during the reaction process. Temperature sensors, such as thermocouples or other forms of temperature sensing components, can be attached between the microfluidic chip 460 and the carrier surface 4211. These sensors can monitor the temperature in the reaction unit of the microfluidic chip 460 in real time. The monitored temperature can be used to adjust the power of the electric heater to ensure that the temperature of the reaction unit of the microfluidic chip 460 is stably maintained within the required range.
[0073] In some embodiments, the temperature control module 440 is configured to provide multiple different temperature zones to the microfluidic chip 460, such that corresponding regions of the microfluidic chip 460 are at different temperatures. Such a microfluidic device 400 can be used, for example, for temperature-variable PCR detection. In some embodiments, the temperature control module 440 is configured to provide a temperature zone to the microfluidic chip 460, such that various regions of the microfluidic chip 460 are at the same temperature. Such a microfluidic device 400 can be used, for example, for isothermal PCR detection.
[0074] In some embodiments, to improve the temperature control accuracy of the temperature control module 440, the following process may also be performed: obtaining the volume V of the sample liquid entering the reaction unit of the microfluidic chip 460, the temperature T required for the reaction, and the type of sample liquid; adjusting the output heating power P of the electric heater of the temperature control module 440 to the reference value P of the output heating power corresponding to the sample liquid of that type at that volume V and that temperature T. ref The real-time temperature T of the sample is obtained through the temperature sensor of the temperature control module 440. real When the real-time temperature T real When the difference ΔT between the actual temperature and the required reaction temperature T exceeds a preset value, the output heating power P is adjusted to ensure that the real-time temperature T is maintained. realThe temperature difference ΔT between the reaction temperature and the required reaction temperature T does not exceed a preset value until the reaction ends. Temperature control here can be achieved using various suitable control methods, such as Proportional-Integral-Differential (PID) control, which are currently known or will be developed in the future. Furthermore, the volume V of the sample liquid entering the reaction unit of the microfluidic chip 460, the required reaction temperature T, and the type of sample liquid are all determined by the specific detection items, the specifications of the microfluidic chip, and its type. In other words, these parameters are actually determined before the reaction begins, and therefore, this information can be quickly obtained, for example, through barcode scanning. Output heating power reference value P. ref The values can be calculated based on the volume V of the sample liquid entering the reaction unit of the microfluidic chip 460, the required reaction temperature T, the specific heat capacity C of the sample liquid, and the density ρ. Alternatively, they can be calibrated through simulated heating experiments during the design and manufacturing process of the microfluidic chip. When in use, they can be obtained by referring to a table. When the real-time temperature T... real When the difference ΔT between the temperature required for the reaction and the temperature T exceeds the preset value, the adjustment range of the output heating power P can be determined according to the actual situation, or the reference value of the adjustment range can be determined by simulating heating experiments during the design and manufacturing process of the microfluidic chip.
[0075] Continue to refer to Figure 14 In some embodiments, the microfluidic device 400 may further include a control module 450, which communicates with the light control module 410, the detection module 430, the movement module 420, and the temperature control module 440, and is configured to control the operation of the light control module 410, the detection module 430, the movement module 420, and the temperature control module 440 to achieve microfluidic movement control, detection control, position control, and temperature control of the microfluidic chip 460. The control module 450 can perform timing control to automatically perform sample introduction, mixing, reaction, detection, and analysis on the microfluidic chip 460. For example, in... Figure 4After the microfluidic chip 100 is fixed on the bearing surface 4211 of the carrier stage 421 of the moving module 420, the control module 450 can control the temperature control module 440 to turn on to preheat the microfluidic chip 100 to the reaction temperature. After the sample to be tested is added to the inlet 101 of the microfluidic chip 101, the sample to be tested reaches each sample dispensing channel 1051-1052 along the sample inlet channel 102 under the capillary force of the capillary pump 103, and then enters the reaction channels 1041-1042 of each reaction unit 110A-110B. At this time, the control module 450 can control the light control module 410 to turn on the light source 411 and control the moving module 420 to change the position of the microfluidic chip 100 relative to the light source 411 so that the light spot of the light source 411 moves on the reaction channels 1041-1042. The control module 450 controls the photocontrol module 410 and the movement module 420 to photo-drive the liquid in the reaction channels 1041-1042 according to the preset reaction process until the reaction is complete. After the reaction is completed, the control module 450 controls the photocontrol module 410 and the movement module 420 to photo-drive the liquid to be detected to the fourth connection point CP41-CP42 and open the communication between the second communication structure 1081-1082 and the third communication structure 1131-1133 and the atmosphere, so that the liquid to be detected can enter the detection channels 1121-1123. Then, the control module 450 controls the movement module 420 to move the detection channels 1121-1123 of the microfluidic chip 100 into the detection field of view of the detection module 430 and controls the detection module 430 to detect it to obtain the detection result.
[0076] Continue to refer to Figure 14 In some embodiments, the microfluidic device 400 may further include a housing 470, within which the aforementioned control module 450, light control module 410, detection module 430, movement module 420, and temperature control module 440 are all housed. A display screen 480 and an operation panel 490, electrically coupled to the control module 450, can be provided on the housing 470 to allow the user to operate the light control module 410, detection module 430, movement module 420, and temperature control module 440. Through the operation panel 490, the user can freely select and adjust the movement path of the stage 421, the start and stop of the light control module 410, the settings of the temperature control module 440, the selection of detection items for the detection module 430, and the start and stop of the detection process. Based on the states of the movement module 420 and the light control module 410, the control module 450 can determine the liquid position in the microfluidic chip 460 and display it on the display screen 480. The display screen 480 may also display the detection results of the detection module 430.
[0077] The microfluidic device disclosed herein achieves contactless actuation of microfluidics within a microfluidic chip through photo-driven microfluidics. It integrates various methodologies for detection onto a single microfluidic chip and provides corresponding detection units for these methods, enabling the performance of multiple methodologies within a single device. This microfluidic device features a small size, low detection cost, and high detection accuracy. It also provides a portable, automated point-of-care testing (POCT) device covering different methodologies, is easy to operate without requiring specialized user skills, and can meet users' daily testing needs.
[0078] It is particularly important to emphasize that the most significant characteristic of PCR detection technology is its ability to significantly amplify trace amounts of DNA, thus its widespread application in fields such as medical testing. However, conventional PCR testing equipment is currently quite bulky, making it difficult to meet the needs of point-of-care testing (POCT). Furthermore, PCR reaction conditions are demanding; inaccurate control can affect test results, therefore samples are typically sent to specialized testing laboratories or clinical laboratories for analysis. In contrast, the microfluidic device disclosed herein, by relocating the PCR detection process within a microfluidic chip, not only reduces sample volume and reaction time but also maintains detection accuracy, providing a POCT device capable of performing PCR detection.
[0079] The terms “left,” “right,” “front,” “back,” “top,” “bottom,” “upper,” “lower,” “high,” “lower,” etc., used in the specification and claims, if present, are for descriptive purposes and not necessarily for describing unchanging relative positions. It should be understood that such terms are interchangeable where appropriate, enabling the embodiments of this disclosure described herein to operate, for example, in orientations different from those shown or otherwise described herein. For example, when the device in the drawings is reversed, a feature previously described as “above” other features may now be described as “below” other features. The device may also be oriented in other ways (rotated 90 degrees or in other orientations), in which case the relative spatial relationships will be interpreted accordingly.
[0080] In the specification and claims, when an element is described as being "on top of," "attached" to, "connected" to, "coupled" to, "coupled to," or "in contact with" another element, the element may be directly located on top of, directly attached to, directly connected to, directly coupled to, directly coupled to, or directly in contact with the other element, or one or more intermediate elements may be present. Conversely, when an element is described as being "directly" located on top of, directly attached to, directly connected to, directly coupled to, directly coupled to, or directly in contact with another element, no intermediate elements are present. In the specification and claims, when a feature is arranged "adjacent" to another feature, it may mean that a feature has a portion overlapping with the adjacent feature or a portion located above or below the adjacent feature.
[0081] As used herein, the term "exemplary" means "serving as an example, instance, or illustration," and not as a "model" to be precisely copied. Any implementation described herein by example is not necessarily to be construed as preferred or advantageous over other implementations. Furthermore, this disclosure is not limited to any theory expressed or implied as given in the art, background, summary of the invention, or detailed description.
[0082] As used herein, the term "substantially" means any minor variation resulting from design or manufacturing defects, device or component tolerances, environmental influences, and / or other factors. The term "substantially" also allows for differences from the perfect or ideal situation due to parasitic effects, noise, and other practical considerations that may exist in the actual implementation.
[0083] Additionally, terms such as “first,” “second,” etc., may be used in this document for reference purposes only and are not intended to be limiting. For example, unless the context clearly indicates otherwise, the words “first,” “second,” and other such numerical terms relating to structures or elements do not imply order or sequence.
[0084] It should also be understood that when the term “including / contains” is used herein, it indicates the presence of the indicated feature, whole, step, operation, unit and / or component, but does not preclude the presence or addition of one or more other features, wholes, steps, operations, units and / or components and / or combinations thereof.
[0085] In this disclosure, the term “provide” is used broadly to cover all ways of obtaining an object, and therefore “provide an object” includes, but is not limited to, “purchasing,” “preparing / manufacturing,” “arranging / setting up,” “installing / assembling,” and / or “ordering” an object.
[0086] As used herein, the term “and / or” includes any and all combinations of one or more of the listed items in association. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of this disclosure. As used herein, the singular forms “a,” “an,” and “the” are also intended to include the plural forms unless the context clearly indicates otherwise.
[0087] Those skilled in the art will recognize that the boundaries between the above operations are merely illustrative. Multiple operations may be combined into a single operation, a single operation may be distributed among additional operations, and operations may be performed with at least partial overlap in time. Moreover, alternative embodiments may include multiple instances of a particular operation, and the order of operations may be changed in various other embodiments. However, other modifications, variations, and substitutions are equally possible. Aspects and elements of all the embodiments disclosed above may be combined in any way and / or in combination with aspects or elements of other embodiments to provide multiple additional embodiments. Therefore, this specification and the accompanying drawings should be considered illustrative rather than restrictive.
[0088] While specific embodiments of this disclosure have been described in detail by way of example, those skilled in the art should understand that the examples are for illustrative purposes only and not intended to limit the scope of this disclosure. The various embodiments disclosed herein can be combined in any way without departing from the spirit and scope of this disclosure. Those skilled in the art should also understand that various modifications can be made to the embodiments without departing from the scope and spirit of this disclosure. The scope of this disclosure is defined by the appended claims.
Claims
1. A microfluidic chip, the microfluidic chip comprising a microfluidic unit, the microfluidic unit comprising: The inlet is configured to receive sample microfluids; The sample inlet channel is configured to communicate with the sample inlet to receive sample microfluids from the sample inlet. A capillary pump is configured to communicate with the injection channel to draw sample microfluids through and out of the injection channel; as well as One or more reaction units, each reaction unit comprising: The annular reaction channel is configured to connect the inlet and the capillary pump via a dispensing channel corresponding to the reaction unit and the inlet channel to receive a preset volume of sample microfluidic fluid corresponding to the reaction unit from the inlet channel. The reaction channel includes a photodeformable material that allows the microfluidic fluid to be driven through the reaction channel by the Laplace pressure difference generated by the asymmetric photodeformation of the reaction channel. The first connecting structure is configured to connect to the reaction channel at one end and remain connected to the atmosphere at the other end, so that the sample microfluidic fluid can self-close the first connecting structure after entering it from the sample dispensing channel through the reaction channel. The first connection point between the sample dispensing channel and the reaction channel and the second connection point between the reaction channel and the first connecting structure are spaced apart from each other along the longitudinal centerline of the reaction channel. Among them, the cross-sectional area of the injection channel is greater than that of the reaction channel, the cross-sectional area of the reaction channel is greater than that of the first connecting structure, the cross-sectional area of the reaction channel is greater than that of the dispensing channel, and the depth of the reaction channel is greater than that of the dispensing channel.
2. The microfluidic chip according to claim 1, wherein, The microfluidic unit also includes a buffer tube connected between the sample inlet channel and the capillary pump, wherein the cross-sectional area of the buffer tube is larger than the cross-sectional area of the sample inlet channel.
3. The microfluidic chip according to claim 1, wherein, The first connecting structure includes an equilibrium channel that is connected to a corresponding reaction channel at one end and to the atmosphere at the other end. The cross-sectional area of the equilibrium channel is smaller than that of the reaction channel, wherein: The end of the equilibrium channel is designed to be open to the atmosphere; or The end of the balancing channel includes a balancing cavity with a vertical through-hole for communication with the atmosphere.
4. The microfluidic chip according to claim 1, wherein, The first connecting structure includes a main trunk that is connected at one end to a corresponding reaction channel and at the other end to the atmosphere, as well as branches with closed ends branching off from the main trunk.
5. The microfluidic chip according to claim 1, wherein, The one or more reaction units are configured to receive sample microfluidics of different preset volumes from the sample inlet channel.
6. The microfluidic chip according to claim 1, wherein, The difference in depth between the sample dispensing channel and the reaction channel is configured to allow the microfluidic fluid to move across the first connection point between the sample dispensing channel and the reaction channel within the reaction channel.
7. The microfluidic chip according to claim 1, wherein, The ratio of the depth of the sampling channel to the depth of the reaction channel is less than 1:
2.
8. The microfluidic chip according to claim 1, wherein, The ratio of the depth of the sampling channel to the depth of the reaction channel is less than or equal to 1:
4.
9. The microfluidic chip according to claim 1, wherein, The photodeformable material is configured to expand in response to light, such that portions of the reaction channel have a larger cross-sectional area when illuminated compared to when not illuminated, thereby driving the microfluidic flow in the reaction channel in the direction of decreasing light intensity; or The photodeformable material is configured to contract in response to light, such that portions of the reaction channel have a smaller cross-sectional area when illuminated compared to when not illuminated, thereby driving the microfluidic in the reaction channel in the direction of increasing light intensity.
10. The microfluidic chip according to claim 1, wherein, The photodeformable material includes a photodeformable liquid crystal polymer material, which includes a photoresponsive linear liquid crystal polymer material with a polycyclooctene main chain and azobenzene side chains.
11. The microfluidic chip according to claim 1, wherein, Pre-prepared reactants are stored at one or more different locations in the reaction channel, and the sample microfluidic can be driven to each of the one or more different locations by the Laplace pressure difference generated by the asymmetric photodeformation of the reaction channel to contact, mix and / or react with the pre-prepared reactants at that location.
12. The microfluidic chip according to claim 1, wherein, Each of some or all of the one or more reaction units further includes: The second connection structure is configured to be connected to the reaction channel at one end and to the atmosphere at the other end; The detection channel is configured to communicate with the reaction channel at one end to receive the microfluidic fluid to be detected from the reaction channel, and to communicate with the atmosphere at the other end via a third communication structure. Specifically, the first distance between the third connection point of the reaction channel and the first connection point along the longitudinal centerline of the reaction channel in a first direction is greater than the minimum distance between the first connection point and the second connection point along the longitudinal centerline of the reaction channel. Conversely, the second distance between the third connection point and the first connection point along the longitudinal centerline of the reaction channel in a second direction opposite to the first direction is greater than the minimum distance between the first connection point and the second connection point along the longitudinal centerline of the reaction channel. In this configuration, the connection between each of the second and third interconnecting structures and the atmosphere is switchable, and... The cross-sectional area of the reaction channel is larger than that of the detection channel.
13. The microfluidic chip according to claim 12, wherein, The detection channels are arranged in a spiral shape.
14. The microfluidic chip according to claim 12, wherein, Each reaction unit includes at least two detection channels spaced apart from each other.
15. The microfluidic chip according to claim 12, wherein, The detection channel is located inside the reaction channel.
16. The microfluidic chip according to claim 12, wherein, The fourth connection point of the detection channel and the reaction channel coincides with the first connection point.
17. The microfluidic chip according to claim 12, wherein, Each of the second and third connected structures includes an opening that can be opened to the atmosphere, and wherein: A baffle is provided at the opening, and the baffle is movable between a first position that closes the opening and a second position that does not close the opening; or A photodeformable material is provided at the opening. The photodeformable material is configured to not close the opening when not exposed to light, but to undergo photodeformation to close the opening when exposed to light, or to close the opening when not exposed to light, but to undergo photodeformation to not close the opening when exposed to light.
18. The microfluidic chip according to any one of claims 1 to 17, comprising: A substrate having an inlet and a groove communicating with the inlet; as well as A photodeformable film attached to a substrate, the photodeformable film at least partially covering the groove to form a closed channel together with the groove, such that the microfluidic fluid can be driven through the closed channel under the Laplace pressure difference generated by the asymmetric photodeformation of the closed channel, the closed channel at least providing the reaction channel.
19. The microfluidic chip according to any one of claims 1 to 17 further comprises a plurality of mutually independent microfluidic units.
20. The microfluidic chip according to any one of claims 1 to 17, wherein, The microfluidic chip is used for at least one of the following: immunoassay, biochemical assay, molecular assay, and polymerase chain reaction assay.
21. A method for operating a microfluidic chip according to any one of claims 1 to 20, comprising: Add sample microfluidic fluid to the injection port to allow the added sample microfluidic fluid to enter the injection channel; After the sample microfluidic self-closes the first connecting structure of each of the one or more reaction units and remains in the injection channel, the sample microfluidic in the reaction channel is separated from the sample microfluidic in the respective dispensing channel corresponding to the one or more reaction units. The sample microfluidic in the reaction channel is then moved in the reaction channel by selectively illuminating the reaction channel locally.
22. A method for operating a microfluidic chip according to any one of claims 12 to 17, comprising: Each of the second and third connected structures is made to be isolated from the atmosphere; Add sample microfluidic fluid to the injection port to allow the added sample microfluidic fluid to enter the injection channel; After the sample microfluidic self-closes the first connecting structure of each of the one or more reaction units and remains in the injection channel, the sample microfluidic in the reaction channel is separated from the sample microfluidic in the respective dispensing channel corresponding to the one or more reaction units. The sample microfluidic in the reaction channel is moved in the reaction channel by selectively illuminating the local area of the reaction channel. After the reaction in the reaction channel is completed, the sample microfluidic in the reaction channel is driven to the fourth connection point between the detection channel and the reaction channel by selectively illuminating the local area of the reaction channel; Each of the second and third connecting structures is connected to the atmosphere, thereby allowing the sample microfluidic in the reaction channel to enter the detection channel.
23. A microfluidic device comprising a microfluidic chip according to any one of claims 1 to 20 and a light source configured to provide illumination to the microfluidic chip to control the movement of microfluidics in the microfluidic chip.
24. The microfluidic device according to claim 23, wherein, The light source is configured to move relative to the microfluidic chip to scan the illumination position on the microfluidic chip; or The light source comprises an array of multiple light sources, each of which has a different illumination position on the microfluidic chip.
25. The microfluidic device according to claim 23, further comprising one of the following: A light-shielding plate is disposed between the microfluidic chip and the light source and configured to allow selective portions of the microfluidic chip's reaction channels to receive light from the light source while the remaining portions do not, or to allow selective portions of the microfluidic chip's reaction channels to not receive light from the light source while the remaining portions do; or An attenuator is disposed between the microfluidic chip and the light source and configured to attenuate the intensity of the light received by a selectable portion of the reaction channel of the microfluidic chip compared to the light received by the remaining portion of the reaction channel.
26. The microfluidic device according to claim 25, wherein, The microfluidic chip and the light source are fixed in place, and The light-shielding plate or light-attenuating plate is movable, allowing for the selection of different selectable portions of the reaction channels of the microfluidic chip.
27. The microfluidic device of claim 23, further comprising a controller, the controller being configured to: After the sample microfluidic self-closes the first connecting structure of each of the one or more reaction units and is still retained in the sample injection channel, the sample microfluidic in the sample injection channel is separated from the sample microfluidic in the respective sample dispensing channel corresponding to the one or more reaction units. The control light source selectively illuminates the reaction channel locally, causing the sample microfluidic in the reaction channel to move in the reaction channel.
28. The microfluidic device according to claim 27, wherein, The microfluidic chip is the microfluidic chip according to any one of claims 12 to 17, and wherein the controller is configured to: Before adding sample microfluidic fluid to the inlet, control is executed to prevent each of the second and third interconnected structures from being connected to the atmosphere. After the sample microfluidic self-closes the first connecting structure of each of the one or more reaction units and is still retained in the sample injection channel, the sample microfluidic in the sample injection channel is separated from the sample microfluidic in the respective sample dispensing channel corresponding to the one or more reaction units. The light source is controlled to selectively illuminate the reaction channel locally, so that the sample microfluidic in the reaction channel moves in the reaction channel. After the reaction in the reaction channel is completed, the light source is controlled to selectively illuminate the local area of the reaction channel, driving the sample microfluidic in the reaction channel to the fourth connection point of the detection channel and the reaction channel; The execution control connects each of the second and third interconnected structures to the atmosphere, thereby allowing the sample microfluidic in the reaction channel to enter the detection channel.
29. A microfluidic device, comprising: A light control module, comprising a light source configured to provide illumination to a microfluidic chip to control the movement of microfluidics within the microfluidic chip, wherein the microfluidics are photo-driven. as well as A moving module is configured to move the microfluidic chip to adjust its relative position to the light source, so that the microfluidic chip is selectively and locally illuminated by the light source, thereby photo-driven the microfluidics within the microfluidic chip. The light control module is fixed above the moving module. The microfluidic chip is the microfluidic chip according to any one of claims 1 to 20.
30. The microfluidic device according to claim 29, further comprising: A detection module, configured to perform detection on the microfluidic chip, The moving module is further configured to move the microfluidic chip to adjust the relative position of the microfluidic chip and the detection module, so that the microfluidic chip is detected by the detection module. The detection module is fixed above the moving module and spaced apart from the light control module.
31. The microfluidic device according to claim 30, wherein, The detection module includes multiple detection units, and the relative arrangement of the multiple detection units corresponds to the relative arrangement of multiple detection areas of the microfluidic chip.
32. The microfluidic device according to claim 31, wherein, The plurality of detection units include a fluorescence detection unit and an absorbance detection unit. The detection point of the fluorescence detection unit is configured to coincide with the light spot of the light source of the light control module. The distance between the absorbance detection unit and the fluorescence detection unit is configured to be the same as the distance between the two detection areas of the microfluidic chip.
33. The microfluidic device according to claim 30, further comprising: A temperature control module is configured to control the temperature of the microfluidic chip, wherein the temperature control module is arranged in the mobile module.
34. The microfluidic device according to claim 33, wherein, The temperature control module is configured to provide multiple different temperature zones to the microfluidic chip, such that the corresponding multiple regions of the microfluidic chip are at different temperatures, and wherein the microfluidic device is used for temperature-dependent polymerase chain reaction detection.
35. The microfluidic device according to claim 33, wherein, The temperature control module is configured to provide a temperature zone to the microfluidic chip, such that all regions of the microfluidic chip are at the same temperature, and wherein the microfluidic device is used for isothermal polymerase chain reaction detection.
36. The microfluidic device according to claim 33, further comprising: A control module communicates with the light control module, the detection module, the movement module, and the temperature control module, respectively, and is configured to control the operation of the light control module, the detection module, the movement module, and the temperature control module to realize the microfluidic chip's microfluidic movement control, the microfluidic chip's detection control, the microfluidic chip's position control, and the microfluidic chip's temperature control.
Citation Information
Patent Citations
Light-driven circulating polymerase chain reaction micro-fluidic device and application thereof
CN112779125A
Micro-fluidic chip with annular reaction channel, micro-fluidic device and micro-fluidic equipment
CN219984717U